© 1996 American Heart Association, Inc.
Articles |
Role of Endothelium-Derived Nitric Oxide in the Modulation of Canine Myocardial Mitochondrial Respiration In Vitro
Implications for the Development of Heart Failure
the Department of Physiology, New York Medical College, Valhalla.
Correspondence to Thomas H. Hintze, PhD, Professor of Physiology, New York Medical College, Valhalla, NY 10595.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The mechanism responsible for the regulation of cardiac function by endogenous nitric oxide (NO) remains unclear. In this investigation, O2 consumption by freshly isolated myocardial muscle segments from the left ventricular free wall of canine hearts was quantified by a Clark-type O2 electrode at 37°C. S-nitroso-N-acetylpenicillamine (SNAP, 9±3% to 50±8%), bradykinin (BK, 14±3% to 30±5%), or carbachol (CCh, 15±4% to 29±4%) significantly attenuated tissue O2 consumption at doses of 10-7 to 10-4 mol/L (mean±SE, P<.05). The effects of BK and CCh, but not SNAP, were blocked by 10-4 mol/L NG-nitro-L-arginine, consistent with both BK and CCh stimulating NO biosynthesis and with SNAP decomposing to release NO, respectively. Similar doses of 8-Br-cGMP caused a respiratory inhibition, but to a lesser extent (9±2% to 14±6%). A mitochondrial uncoupler, 2,4-dinitrophenol (at 1 mmol/L), blocked the effects of 8-Br-cGMP, but not those of SNAP, BK, or CCh, suggesting that the major site of action of NO is on mitochondrial electron transport. Myocardial muscle from dogs with pacing-induced heart failure had a basal O2 consumption rate of 251±21 nmol·min-1·g-1, which was 54% higher than the rate seen in muscle from normal healthy canine hearts. The inhibitory effects of BK and CCh on O2 consumption were not observed in failing cardiac tissue, but SNAP showed an unaltered inhibitory effect. Therefore, our results indicate that NO released from microvascular endothelium by BK, stimulation of muscarinic receptors, and perhaps flow velocity may play an important physiological role in the control of cardiac mitochondrial respiration, and the loss of this regulatory function may contribute to the development of heart failure.
Key Words: bradykinin • cGMP • oxygen consumption • microvascular endothelium • cardiac dysfunction
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Coronary blood vessels in the microcirculation are adjacent to myocardial muscle cells, where the distance between myocytes and the nearest capillary is on average <8 µm.1 2 This short diffusing distance suggests that vasoactive factors released from microvascular endothelium may affect the adjacent myocardium. Among these vasoactive substances is NO, whose well-known physiological functions include regulation of vascular tone, neuronal communication, and host defense. The short half-life of NO may limit its function; nevertheless, it is very lipophilic and thereby readily diffuses into intracellular target sites. In fact, the predicted mean diffusion distance of NO under physiological conditions is 200 to 600 µm,3 suggesting that endothelium-derived NO from the microcirculation could affect nearby tissue function, particularly in cardiac muscle, where the ratio of microvessels to myofibrils is
1:1.4 We have previously demonstrated that canine coronary microvessels are capable of generating NO when stimulated with acetylcholine or BK.5 Studies with isolated perfused hearts recently showed that 5-hydroxytryptamine stimulated NO release from the coronary microvasculature.6 These studies suggest that NO biosynthesis is present in the microvascular endothelium as well as in large vessels.
Metal-containing proteins, particularly iron-containing proteins such as heme proteins and those with iron-sulfur complexes, serve as a major intracellular target for NO. Typical examples of heme proteins are guanylate cyclase and hemoglobin; those proteins with iron-sulfur clusters include mitochondrial aconitase and complexes I and II in the electron transport chain. The interactions of NO with these iron-containing proteins can lead to either a stimulation or an inhibition of the proteins' normal function.
Before the discovery of NO formation in endothelium, an undefined substance produced by activated macrophages was observed to suppress O2 consumption by bacteria and cultured mammalian cells.7 8 Recent studies suggest that this macrophage-related substance is NO.9 10 Thus, NO released under inflammatory conditions may be beneficial for host defense due to its ability to suppress bacterial respiration.
Recent in vivo studies with canine skeletal muscle, from our laboratory11 and others,12 have suggested that endogenous NO production may regulate tissue O2 consumption, in addition to its classic vasodilator action. Increasing evidence also indicates that NO plays an important role in the control of myocyte inotropic state.13 14 Therefore, the present investigation was carried out to determine whether endogenously generated NO could regulate O2 consumption of myocardial muscle under physiologically relevant conditions and whether this relationship between NO and muscle respiration would be altered after the development of heart failure.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The primary aim of this study was to assess the role of NO in the control of cellular respiration of isolated myocardial muscle from normal and failing canine hearts. Two groups of adult mongrel dogs, one normal (n=17) and one with pacing-induced heart failure (n=7), were used in the experiments.
Materials
BK, CCh, 8-Br-cGMP, DNP, atropine methyl bromide (atropine), and L-arginine were purchased from Sigma Chemical Company. L-NNA was obtained from Aldrich Chemical Company, and sodium cyanide from JT Baker Chemical Company. SNAP was synthesized as described15 and N-acetylpenacillamine (10-4 mol/L) was used as a control. DNP was dissolved in dimethyl sulfoxide. All other materials were dissolved in Krebs' solution containing (mmol/L) NaCl 118, KCl 4.7, CaCl2 1.5, NaHCO3 25, KH2PO4 1.2, MgSO4 1.1, and glucose 5.6, pH 7.4.
Animal Preparation
Heart failure was induced by chronic rapid LV pacing for 4 weeks in chronically instrumented conscious dogs, and hemodynamic data from these awake dogs were obtained using previously implanted catheters and transducers, as described in detail.5 All dogs were killed with pentobarbital sodium (25 mg/kg IV), and the heart was immediately removed and placed in cold buffer.
Preparation of Muscle Slices
Myocardial muscle was isolated from the left ventricle (free wall only) of hearts immediately after the dogs were killed. The muscle was freed of epicardium, endocardium, connective tissue, fat, and large arteries and was cut into 30- to 50-mg segments. Prior to studies of tissue respiration, these muscle segments were bathed at 37°C for 2 hours in Krebs' solution, in which 21% O2/5% CO2/75% N2 was continuously bubbled.
Respiration Measurements
O2 uptake by muscle slices was measured polarographically with a Yellow Springs Instrument Co apparatus consisting of a YSI model 5300 biological O2 monitor and a Clark-type O2 electrode (YSI 5331). O2 consumption studies were performed at 37°C in a stirred 1- to 10-mL bath (YSI 5301) containing 3 mL air-saturated Krebs' solution buffered with 10 mmol/L HEPES (pH 7.4). Tissue respiration was calculated as the rate of decrease in O2 concentration following the addition of muscle slices, assuming an initial O2 concentration of 224 nmol/mL,16 and was expressed as nanomoles O2 consumed per minute per gram tissue. O2 uptake by muscle slices was only monitored before one third of the O2 was consumed, and any spontaneous changes in the electrode recording in the absence of tissue were subtracted from each measured rate of tissue O2 consumption. The typical observation time for each dose of an agent was 5 minutes, and new muscle segments were used for each drug examined. Sodium cyanide (1 mmol/L) was added at the end of each respiration measurement to confirm that changes in O2 consumption were from mitochondrial sources.
Effects of Examined Agents on Tissue Respiration
SNAP, BK, CCh, or 8-Br-cGMP was added to the tissue bath in a cumulative concentration-dependent (10-7 to 10-4 mol/L) manner and their effects on muscle O2 consumption were recorded. The effects of SNAP, BK, and CCh were examined in the presence of 10-4 mol/L L-NNA; the effect of L-NNA alone on tissue respiration was also studied. The response to the highest dose of CCh was examined in the presence of 10-4 mol/L atropine. DNP (1 mmol/L) was added to the tissue bath in the presence or absence of individual doses of SNAP, CCh, BK, BK+L-NNA, or 8-Br-cGMP, and the change in O2 consumption was reported.
Statistical Analysis
All data are reported as mean±SE, and n in all instances is the number of different animals studied. Differences in the mean values were analyzed using unpaired and, where appropriate, paired Student's t tests. Significance was assumed at P<.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
NO-Mediated Inhibition of O2 Consumption in Normal Myocardial Muscle
An actual recording of tissue O2 consumption is shown in Fig 1
, and calculated O2 consumption is shown in Table 1. The NO-releasing agent SNAP15 significantly inhibited O2 consumption by myocardial muscle slices from normal dogs by 9±3% to 50±8% over the dose range 10-7 to 10-4 mol/L (Fig 2A). In contrast, SNAP had no effect on tissue O2 consumption (1.8±1.7%) even at 10-4 mol/L. BK, a stimulus of endogenous NO generation,17 18 also reduced muscle respiration by 14±3% to 30±5% over a similar dose range (Fig 2B). Similar doses of CCh (not shown), another probe to stimulate endogenous NO formation,17 18 significantly decreased tissue respiration by 15±4% to 29±4% (n=5, all P<.05 versus control). The inhibitory effect of the highest dose (10-4 mol/L) of CCh examined was abolished by pretreatment with 10-4 mol/L atropine, a specific antagonist of muscarinic cholinergic receptors (n=5, not shown). Pretreatment with L-NNA (10-4 mol/L), a specific NO synthase inhibitor, had no effect on the suppression of muscle respiration by SNAP (Fig 2A), but abolished the reduction of tissue respiration by BK (Fig 2B) and CCh (n=5, not shown). L-NNA itself did not alter muscle respiration at a dose of 10-4 mol/L (n=12). As shown in Fig 1, sodium cyanide blocked the decrease in bath O2 concentration, indicating that most of the O2 consumption was dependent on mitochondrial function.
|
|
|
, control, n=9; 
, L-NNA, n=5). B, L-NNA abolished BK-induced suppression of muscle respiration (
DNP-Elicited Elevation in O2 Uptake by Normal Myocardial Muscle
Muscle respiration was significantly increased (99±16%, P<.01) by 1 mmol/L DNP, a mitochondrial uncoupler between oxidative phosphorylation and electron transport (Fig 3). After muscle segments were pretreated with SNAP, CCh, or BK at a dose of 10-5 mol/L, the effect of DNP on tissue respiration was attenuated (Fig 3). Pretreatment with L-NNA attenuated the inhibitory effect of BK on DNP-induced increase in O2 consumption (Fig 3).
|
Effect of 8-Br-cGMP on O2 Consumption by Normal Myocardial Muscle
A stable cGMP analogue, 8-Br-cGMP, significantly reduced cardiac muscle respiration by 9±2% to 14±6% over the dose range 10-7 to 10-4 mol/L (n=6, P<.05), which was significantly less than the inhibitory effects of BK or CCh on O2 consumption. In addition, 8-Br-cGMP did not significantly alter DNP-elicited increases in muscle respiration, as seen with BK or CCh (Fig 3
).
Induction of Heart Failure
Hemodynamic changes before and after chronic LV pacing for 4 weeks are summarized in Table 2. All values after heart failure (after 4-week pacing) were significantly different from those in the prepacing state. After the development of heart failure, LV end-diastolic pressure and heart rate increased by 391±130% and 48±11%, respectively, while LV systolic pressure, LV dP/dt, and mean arterial pressure decreased by 24±4%, 51±6%, and 19±3%, respectively. These characteristics, as well as the presence of ascites, edema, dyspnea, and protein wasting, indicate a severe form of heart failure. This model of heart failure resembles a dilated form of cardiac myopathy, as described.5 19 20
|
Respiration Studies in Failing Myocardial Muscle
The O2 consumption rate of failing myocardial muscle was 251±21 nmol·min-1·g-1, significantly higher than that of normal myocardial muscle, 162±12 nmol·min-1·g-1 (P<.01). The actual changes in O2 consumption after addition of NO-releasing agents are shown in Table 1.
Effect of SNAP on O2 consumption by failing muscle was very similar to that of normal muscle before or after L-NNA (Fig 4A). However, the responses of failing cardiac tissue to stimulation of endogenous NO synthesis with BK (Fig 4B) or CCh (n=5, not shown) were not observed. L-NNA alone did not alter failing muscle respiration at a dose of 10-4 mol/L (n=5).
|
DNP-Elicited Elevation in O2 Uptake by Failing Myocardial Muscle
The effect of DNP on failing cardiac muscle respiration was very similar to that of normal muscle; the increase was 106±15% (Fig 5). SNAP attenuated the increased O2 consumption induced by DNP, but BK or CCh did not suppress DNP-elicited elevation in tissue respiration (Fig 5).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The major finding of the present study with normal myocardial muscle was that endogenous endothelium-derived NO could attenuate mitochondrial respiration of adjacent myocytes. SNAP, which spontaneously decomposes to release NO,15 significantly suppressed O2 consumption by myocardial muscle. Activation of endothelial BK2 receptors by BK and of endothelial cholinergic muscarinic type 2 receptors by CCh, two probes that stimulate endogenous NO synthesis in blood vessels,17 18 resulted in a significant inhibition of O2 uptake by myocardial muscle. These inhibitory effects of BK and CCh were completely reversed by L-NNA, a potent inhibitor of NO biosynthesis. These results demonstrate that NO, derived from either exogenous or endogenous sources, can modulate cellular respiration.
L-NNA alone did not alter O2 consumption by isolated myocardial muscle. One interpretation is that shear stress and transmural pressure, the most important factors for NO synthesis in vivo,21 do not exist in this in vitro model. Alternatively, physiologically relevant levels of NO (ie, 1 to 10 nmol/L) in unstimulated blood vessels may not be sufficient to significantly modulate muscle respiration. However, NO released by stimuli would be much higher and thus could alter tissue respiration. It has been reported, for instance, that NO released from BK-stimulated aorta, as measured by an NO-electrode, increased up to 1300 nmol/L.22
BK2 receptors have not been identified on cardiac myocytes. Although there are muscarinic receptors on myocytes, it has not yet been established whether a constitutive NO synthase is present in these cells. Even though it has been reported that cytokines induced NO synthase gene expression in cardiac myocytes,23 24 it is unlikely that significant NO production by this inducible isoform is expressed under the conditions of the present study, since L-NNA did not directly alter O2 consumption. Alternatively, NO may be produced by the constitutive type III NO synthase in myocytes,25 26 and this NO would have effects on O2 consumption similar to those of endothelial NO. Moreover, NO released by physiological stimulators such as shear stress may have a tonic effect on tissue respiration that remains to be defined.
There is a well-established role for cGMP in many NO-mediated responses, especially cGMP-mediated vasodilation. cGMP exerts negative inotropic, chronotropic, and metabolic effects on cardiac myocytes.13 14 27 Increased myocardial cGMP levels have been shown to reduce myocardial O2 consumption.28 In our study, 8-Br-cGMP, a stable and tissue-permeable analogue of cGMP, had a much smaller inhibitory effect on cardiac muscle respiration than BK or CCh, suggesting that this respiratory inhibition by NO may not be secondary to cGMP-mediated signal transduction. Other studies29 30 have also shown that the effect of nitroprusside, an NO-releasing agent, on O2 consumption was not well correlated with increased cGMP levels.
In this study, application of DNP, an uncoupler of mitochondrial electron transport from oxidative phosphorylation, abolished the respiratory inhibition elicited by 8-Br-cGMP, but not that of SNAP, BK, or CCh in normal cardiac tissue. These effects of DNP suggest that the respiratory inhibition elicited by NO may be mainly due to a direct effect on the mitochondrial electron transport chain rather than an effect secondary to cGMP-mediated extramitochondrial responses. Nonetheless, cGMP-mediated cellular responses may contribute somewhat to this respiratory inhibition via a reduced ATP utilization by myocardial muscle. These results with DNP support our conclusion that NO has an important physiological role in modulating mitochondrial function in the heart. These results were consistent with studies on activated macrophages,7 8 in which NO inhibited mitochondrial aconitase, a key enzyme of the Krebs cycle, and NADH-ubiquinone oxidoreductase (complex I) and succinate-ubiquinone oxidoreductase (complex II) in the mitochondrial electron transport chain, and with other studies31 32 33 34 suggesting an action of NO on cytochrome c oxidase (complex IV), the terminal enzyme in the mitochondrial electron transport chain. The respiratory inhibition on cytochrome c oxidase occurred within the nanomolar range,34 suggesting that this is a very sensitive site for NO action on a mitochondrial enzyme. It is believed that NO reduces the activities of these mitochondrial enzymes via nitrosylation of the iron-sulfur centers of aconitase and complexes I and II35 and by interacting with the heme group of cytochrome c oxidase.31 32 33 34
Increasing evidence suggests that NO can alter myocyte shortening,13 14 and this has been interpreted to be a negative inotropic effect subsequent to increased cGMP levels. This inotropic function of NO may also partially come from a direct modulation of mitochondria by NO. If mitochondrial function is depressed by elevated NO levels, ATP synthesis needed for force development is very likely to be reduced, resulting in a negative inotropic effect. The effect of 8-Br-cGMP on O2 consumption indicates the presence of a separate mechanism, albeit small, through which cGMP (and NO) can control tissue respiration through a change in the energy consumption, in addition to direct action of NO on mitochondrial electron transport.
The inactivation of mitochondrial enzymes (ie, complexes I, II, and ATPase)36 and aconitase37 is also seen with peroxynitrite (ONOO-), a highly oxidizing free radical from the interaction of NO with superoxide anion (O2-). Since peroxynitrite is usually generated in pathological conditions and there are existing and highly efficient superoxide scavenging systems (ie, superoxide dismutase), NO-induced respiratory suppression in this study is unlikely to be due to the effect of peroxynitrite, although we did not directly address this question.
The second major finding in the present study is that O2 consumption by myocardial muscle from failing hearts was not suppressed by stimulation of endogenous NO synthesis (by BK and CCh), and neither BK nor CCh attenuated DNP-induced increases in tissue respiration of the failing muscle, unlike that of normal myocardial muscle. Nonetheless, the effects of SNAP on O2 consumption by failing myocardial muscle were very similar to those of normal muscle. These results suggest that there may be some defect in NO biosynthesis in blood vessels after the development of heart failure. This theory is consistent with our previous studies on nitrite production by microvessels from failing hearts of dogs and humans5 and on the expression of endothelial NO synthase mRNA in blood vessels in dogs with heart failure38 and studies on coronary vasodilator response to acetylcholine injection in humans.39 All of these studies suggest that there is a defect in the ability of coronary blood vessels to produce NO after the development of heart failure.
Interestingly, the basal O2 consumption rate of failing myocardial muscle was found to be 54% higher than that of normal muscle in the present study, consistent with that seen in patients with heart failure, suggesting that the loss of NO production may contribute to the elevated O2 consumption rate. Because of an inability to alter basal O2 consumption in tissue from normal or failing hearts with L-NNA, the role of NO in this response is still open to question. However, since O2 consumption was increased in the failing hearts, it is unlikely that NO production is elevated, as would occur after cytokine activation. Therefore, these results suggest that endothelial dysfunction and the loss of NO biosynthesis correlate with the development of heart failure. We have recently speculated,40 on the basis of our own data5 and the data of others,41 that NO generation is elevated during the initial phases of the development of cardiac dysfunction, perhaps as a compensatory mechanism, and disappears after a prolonged period of heart failure. Most forms of heart failure are initially characterized by elevated coronary blood flow due to the increased metabolic demand on the heart caused by either a pressure or volume overload. This elevated coronary blood flow may initially be elicited by local accumulation of metabolites, such as adenosine, leading to increased shear stress and subsequently enhanced NO synthesis, which causes a further dilation. If NO disappears from the coronary circulation as part of the dysfunction leading to heart failure or as a consequence of the disease process, then an important vasodilator mechanism will be absent, and this may further exacerbate the cardiac and vascular dysfunction. The present study suggests that the loss of NO from blood vessels after heart failure will also result in uncoupling of the control of mitochondrial respiration by NO.
It is possible that a significant amount of NO can come from the myocytes, even though we have attributed NO production primarily to coronary microvessels. We have attempted to discern the contribution of the remaining myocytes after sieving microvessels from either normal or failing canine hearts. We have also tried to measure NO production in pieces of cardiac tissue containing both myocytes and blood vessels. In neither case were we able to measure a basal NO production or stimulated production that could be blocked by L-NNA. This may indicate that the myocytes are damaged during our isolation of blood vessels, that the myocytes produce relatively low amounts of NO, and that it is necessary to concentrate the microvessels to quantitate NO production. Be that as it may, because NO is a freely diffusible gas, altered NO production by myocytes would have qualitatively similar effects on mitochondrial function as long as the diffusion distance was not limiting. NO production would still have to decrease to be consistent with our data on basal O2 consumption in the failing heart.
The segments of cardiac tissue in which we measured O2 consumption totaled about 50 mg per incubate. This approach allowed for a maximum surface area for diffusion of O2. Whether the muscle cells were contracting or not is impossible to say, since we did not measure force generation. As a result, basal O2 consumption should have been very low. Experiments were also conducted in the presence of DNP, and it is doubtful that these tissue segments could contract, owing to the lack of available ATP. Nevertheless, our studies clearly indicate a new potential physiological mechanism of action of NO. Fibrous tissue is known to be present after pacing-induced heart failure, as we have recently reported.42 This could not account for the increase in O2 consumption, however, since the myocyte mass per gram of tissue should have fallen, even if there was myocyte hypertrophy. If anything, this would lead to an underestimation of the O2 consumption per myocyte in our studies.
In summary, the regulation of mitochondrial respiration in myocardial muscle by endothelial-derived NO or perhaps myocyte-derived NO may be an additional physiologically important function of this molecule. We have already shown increased NO production by canine coronary microvessels on acetylcholine or BK stimulation, using nitrite as a measurement of NO production.5 Similarly, measurement of coronary sinus nitrite sampling showed that 5-hydroxytryptamine stimulated NO release from coronary microvasculature in vivo.6 On the basis of these and our own studies, we suggest that coronary microvascular endothelium is capable of releasing NO to modulate nearby myocardial cell function. Since the heart is richly perfused through the coronary microcirculation and capillary endothelial cells have a large surface area, the microvascular endothelium is likely to serve as an enormous source of NO to regulate parenchymal cell metabolism.
In our recent study43 in dogs after brief exercise training, the regulation of tissue O2 consumption by NO and the upregulation of endothelial NO synthase mRNA were also apparent, further suggesting a role for NO in optimizing O2 utilization. This modulation of mitochondrial function by NO may be universal, based on the studies in macrophages,7 8 rat hepatocytes,44 vascular smooth muscle,45 articular chondrocytes,46 skeletal muscle,47 and myocardium in the present study. On the other hand, the modulation of mitochondrial respiration by endogenously generated NO suggests that inappropriately elevated NO production under pathological conditions, as occurs after cytokine induction, could result in a negative inotropic effect, cell death, and overt tissue dysfunction.48 Because mitochondrial ATP production from oxidative phosphorylation is so tightly coupled to cardiac contraction, a reduction in ATP production due to NO modulation of O2 consumption would be difficult to separate from an NO-mediated effect on the contractile apparatus, reduced shortening, or inotropic state.
|
Selected Abbreviations and Acronyms |
|---|
|
-nitro-L-arginine
|
Acknowledgments |
|---|
This work was supported by grants PO-1-HL 40231, HL 31069, HL 50142, and HL 53053 from the National Heart, Lung, and Blood Institute.
Received April 15, 1996; accepted May 22, 1996.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Randall WC. Anatomy of blood circulation. In: Abramson DI, Dobrin PB, eds. Blood Vessels and Lymphatics in Organ Systems. Orlando, Fla: Academic Press Inc; 1984:319-326.
2. Rose CP, Goresky CA. Interactions between capillary exchange, cellular entry, and metabolic sequestration processes in the heart. In: Handbook of Physiology, Cardiovascular System, Microcirculation. Bethesda, Md: American Physiological Society; 1984:781-798.
3. Knowles RG, Moncada S. Nitric oxide as a signal in blood vessels. Trends Biochem Sci. 1992;17:399-402.[Medline] [Order article via Infotrieve]
4.
Rakusan K, Flanagan MF, Geva T, Southern J, Van Praagh R. Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy. Circulation. 1992;86:38-46.
5.
Wang J, Seyedi N, Xu XB, Wolin MS, Hintze TH. Defective endothelium-mediated control of coronary circulation in conscious dogs after heart failure. Am J Physiol.. 1994;266:H670-H680.
6. Shah AM, Fort S, Siney L, Smith JA, Lewis MJ. Endothelium-derived relaxing factor modulates the duration of myocardial contraction. Circulation. 1991;84(suppl II):II-308. Abstract.
7.
Granger DL, Lehninger AL. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol. 1982;95:527-535.
8. Drapier JC, Hibbs JB. Murine cytotoxic activated macrophages inhibit aconitase in tumor cells: inhibition involves the iron-sulfur prosthetic group and is reversible. J Clin Invest. 1986;78:790-797.
9. Marletta MA, Yoon PS, Iyengar RD, Leaf C, Wishnok JS. Macrophage oxidation of L-arginine to nitrate and nitrite: nitric oxide is an intermediate. Biochem. 1988;27:8706-8711.[Medline] [Order article via Infotrieve]
10. Hibbs JB, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988;157:87-94.[Medline] [Order article via Infotrieve]
11.
Shen W, Xu X, Ochoa M, Zhao G, Wolin MS, Hintze TH. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. Circ Res. 1994;75:1086-1095.
12.
King CE, Melinyshyn MJ, Mewburn JD, Curtis SE, Winn MJ, Cain SM, Chapler CK. Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis. J Appl Physiol. 1994;76:1166-1171.
13.
Balligand J-L, Kelly RA, Marsden PA, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci U S A. 1993;90:347-351.
14.
Brady AJB, Warren JB, Poole-Wilson PA, Williams TJ, Harding SE. Nitric oxide attenuates cardiac myocyte contraction. Am J Physiol. 1993;265:H176-H182.
15.
Ignarro LJ, Lippton H, Edwards JC, Baricos WH, Hyman AL, Kadowitz PJ, Gruetter CA. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981;218:739-749.
16. Umbreit WW, Burris RH, Stauffer JF. The solubility of oxygen. In: Manometric Techniques. 4th ed. Minneapolis, Minn: Burgess Pub Co; 1964:5-6.
17.
Vanhoutte PM. Endothelium and control of vascular function. Hypertension. 1989;13:658-667.
18. Moncada S. The L-arginine:nitric oxide pathway. Acta Physiol Scand. 1992;145:201-227.[Medline] [Order article via Infotrieve]
19.
Armstrong PW, Stopps TP, Ford SE, deBold AJ. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circulation. 1986;74:1075-1084.
20.
Wilson JR, Douglas P, Hickey WF, Lanoce V, Ferraro N, Muhammad A, Reichek N. Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. Circulation. 1987;75:857-867.
21. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109-142.[Medline] [Order article via Infotrieve]
22. Malinski T, Taha Z. Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. Nature. 1992;358:676-678.[Medline] [Order article via Infotrieve]
23. Schulz R, Nava E, Moncada S. Induction and potential biological relevance of a Ca2+-independent nitric oxide synthase in the myocardium. Br J Pharmacol. 1992;105:575-580.[Medline] [Order article via Infotrieve]
24. Balligand J-L, Ungureanu D, Kelly RA, Kobzik L, Pimental D, Michel T, Smith TW. Abnormal contractile function due to induction of nitric oxide synthesis in rat myocytes follows exposure to activated macrophage-conditioned medium. J Clin Invest. 1993;91:2314-2319.
25.
Balligand J-L, Kobzik L, Han X, Kaye DM, Belhassen L, O'Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxide–dependent parasympathetic signaling is due to activation of constitutive endothelial (Type III) nitric oxide synthase in cardiac myocytes. J Biol Chem. 1995;270:14582-14586.
26. Belhassen L, Kelly RA, Smith TW, Balligand J-L. Nitric oxide synthase (NOS 3) and contractile responsiveness to adrenergic and cholinergic agonists in the heart. J Clin Invest. 1996;97:1908-1915.[Medline] [Order article via Infotrieve]
27. Lohmann SM, Fischmeister R, Walter U. Signal transduction by cGMP in heart. Basic Res Cardiol. 1991;86:503-514.[Medline] [Order article via Infotrieve]
28. Weiss HR, Rodriguez E, Tse J, Scholz PM. Effect of increased myocardial cyclic GMP induced by cyclic GMP-phospodiesterase inhibition on oxygen consumption and supply of rabbit hearts. Clin Exp Pharmacol Physiol. 1994;21:607-614.[Medline] [Order article via Infotrieve]
29.
Weiss HR, Rodriguez E, Tse J. Relationship between cGMP and myocardial O2 consumption is altered in T4 -induced cardiac hypertrophy. Am J Physiol. 1995;268:H686-H691.
30. Lu X, Wei HM, Yospin J, Weiss HR. Effect of nitroprusside on regional cerebral cyclic GMP, blood flow and O2 consumption in rat. Brain Res. 1995;669:35-40.[Medline] [Order article via Infotrieve]
31. Erecinska M, Wilson DF. Inhibitors of cytochrome c oxidase. Pharmacol Ther. 1980;8:1-20.
32. Cleeter MWJ, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AHV. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide: implications for neurodegenerative diseases. FEBS Lett. 1994;345:50-54.[Medline] [Order article via Infotrieve]
33. Schweizer M, Richter C. Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun. 1994;204:169-175.[Medline] [Order article via Infotrieve]
34. Brown GC, Cooper CE. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 1994;356:295-298.[Medline] [Order article via Infotrieve]
35.
Lancaster JR, Hibbs JB. EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci U S A. 1990;87:1223-1227.
36. Radi R, Rodriguez M, Castro L, Telleri R. Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys. 1994;308:89-95.[Medline] [Order article via Infotrieve]
37.
Hausladen A, Fridovich I. Superoxide and peroxynitrite inactivate aconitase, but nitric oxide does not. J Biol Chem. 1994;269:29405-29408.
38.
Smith CJ, Sun D, Hoegler C, Roth BS, Zhang X, Zhao G, Xu X, Kobari Y, Pritchard K Jr, Sessa WC, Hintze TH. Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res. 1996;78:58-64.
39.
Treasure CB, Vita JA, Cox DA, Fish RD, Gordon JB, Mudge GH, Colucci WS, Sutton MG, Selwyn AP, Alexander RW, Ganz P. Endothelium-dependent dilation of coronary microvasculature is impaired in dilated cardiomyopathy. Circulation. 1990;81:772-779.
40. Hintze TH, Shen W, Seyedi N, Zhao G. Potential roles for changes in coronary and myocyte nitric oxide production in the development of heart failure. Heart Failure. 1994;10:116-125.
41. O'Murchu B, Miller VM, Perrella MA, Burnett JC. Increased production of nitric oxide in coronary arteries during congestive heart failure. J Clin Invest. 1994;93:165-171.
42.
Kajstura J, Zhang X, Liu Y, Szoke E, Cheng W, Olivetti G, Hintze TH, Anversa P. The cellular basis of pacing-induced dilated cardiomyopathy: myocyte cell loss and myocyte cellular hypertrophy. Circulation. 1995;92:2306-2317.
43.
Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994;74:349-353.
44.
Stadler J, Billiar TR, Curran RD, Stuehr DJ, Ochoa JB, Simmons RL. Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes. Am J Physiol. 1991;260:C910-C916.
45.
Geng Y, Hansson GK, Holme E. Interferon-
and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells. Circ Res. 1992;71:1268-1276.
46. Srefanovic-Racic M, Stedler J, Georgescu HI, Evans CH. Nitric oxide and energy production in articular chondrocytes. J Cell Physiol. 1994;159:274-280.[Medline] [Order article via Infotrieve]
47.
Shen W, Hintze TH, Wolin MS. Nitric oxide: an important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumption. Circulation. 1995;92:3505-3512.
48. Pinsky DJ, Cai B, Yang X, Rodriguez C, Sciacca RR, Cannon PJ. The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor J. J Clin Invest. 1995;95:677-685.
This article has been cited by other articles:
 |
|
 |
|
  S. Gao, C.-L. Long, R.-H. Wang, and H. Wang KATP activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function Cardiovasc Res, August 1, 2009; 83(3): 444 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Heinzel, P. Gres, K. Boengler, A. Duschin, I. Konietzka, T. Rassaf, J. Snedovskaya, S. Meyer, A. Skyschally, M. Kelm, et al. Inducible Nitric Oxide Synthase Expression and Cardiomyocyte Dysfunction During Sustained Moderate Ischemia in Pigs Circ. Res., November 7, 2008; 103(10): 1120 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Hall and D. Attwell Assessing the physiological concentration and targets of nitric oxide in brain tissue J. Physiol., August 1, 2008; 586(15): 3597 - 3615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Williams, T. Rincon-Skinner, D. Sun, Z. Wang, S. Zhang, X. Zhang, and T. H. Hintze Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2479 - H2486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhu, B. Liu, S. Zhou, Y.-R. Chen, Y. Deng, J. L. Zweier, and G. He Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1442 - H1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Cooper and C. Giulivi Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology Am J Physiol Cell Physiol, June 1, 2007; 292(6): C1993 - C2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Davidson and M. R. Duchen Endothelial Mitochondria: Contributing to Vascular Function and Disease Circ. Res., April 27, 2007; 100(8): 1128 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Suematsu, C. Ojaimi, S. Kinugawa, Z. Wang, X. Xu, A. Koller MD, F. A. Recchia, and T. H. Hintze Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing Nitric Oxide Bioavailability Through Oxidative Stress Circulation, January 16, 2007; 115(2): 255 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Parent, N. Leblanc, and M. Lavallee Nitroglycerin reduces myocardial oxygen consumption during exercise despite vascular tolerance Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1226 - H1234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sun, O. A. Carretero, J. Xu, N.-E. Rhaleb, F. Wang, C. Lin, J. J. Yang, P. J. Pagano, and X.-P. Yang Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate-Salt Hypertension Hypertension, December 1, 2005; 46(6): 1355 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinugawa, J. Zhang, E. Messina, E. Walsh, H. Huang, P. M. Kaminski, M. S. Wolin, and T. H. Hintze gp91phox-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H862 - H867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yaoita, K. Yoshinari, K. Maehara, M. Sando, K. Watanabe, and Y. Maruyama Different Effects of a High-Cholesterol Diet on Ischemic Cardiac Dysfunction and Remodeling Induced by Coronary Stenosis and Coronary Occlusion J. Am. Coll. Cardiol., June 21, 2005; 45(12): 2078 - 2087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinugawa, H. Huang, Z. Wang, P. M. Kaminski, M. S. Wolin, and T. H. Hintze A Defect of Neuronal Nitric Oxide Synthase Increases Xanthine Oxidase-Derived Superoxide Anion and Attenuates the Control of Myocardial Oxygen Consumption by Nitric Oxide Derived From Endothelial Nitric Oxide Synthase Circ. Res., February 18, 2005; 96(3): 355 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshinari, H. Yaoita, K. Maehara, and Y. Maruyama Different therapeutic responses to treadmill exercise of heart failure due to ischemia and infarction in rats Cardiovasc Res, February 1, 2005; 65(2): 457 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fischer, S. Rossa, U. Landmesser, S. Spiekermann, N. Engberding, B. Hornig, and H. Drexler Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death Eur. Heart J., January 1, 2005; 26(1): 65 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, G. Gong, Y. Ye, T. Guo, A. Mansoor, Q. Hu, K. Ochiai, J. Liu, X. Wang, Y. Cheng, et al. Nitric oxide regulation of myocardial O2 consumption and HEP metabolism Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H310 - H316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, C. Cheng, N. Zorko, S. Cronin, Y.-R. Chen, and J. L. Zweier Biphasic modulation of vascular nitric oxide catabolism by oxygen Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2421 - H2426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Walsh, H. Huang, Z. Wang, J. Williams, R. de Crom, R. van Haperen, C. I. Thompson, D. J. Lefer, and T. H. Hintze Control of myocardial oxygen consumption in transgenic mice overexpressing vascular eNOS Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2115 - H2121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al. Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase Circulation, October 5, 2004; 110(14): 1933 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Nordhaug, T. Steensrud, E. Aghajani, C. Korvald, and T. Myrmel Nitric oxide synthase inhibition impairs myocardial efficiency and ventriculo-arterial matching in acute ischemic heart failure Eur J Heart Fail, October 1, 2004; 6(6): 705 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Paulus and J. G. F. Bronzwaer Nitric oxide's role in the heart: control of beating or breathing? Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H8 - H13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patterson, M. S. Runge, and N. Madamanchi Younger Than Yesterday: Is Vascular Senescence a Two-Way Street? Circ. Res., April 2, 2004; 94(6): 703 - 705. [Full Text] [PDF]
|
|
|
|
|
|
D. Tonduangu, L. Hittinger, B. Ghaleh, P. Le Corvoisier, L. Sambin, S. Champagne, T. Badoual, F. Vincent, A. Berdeaux, B. Crozatier, et al. Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs Circulation, January 6, 2004; 109(1): 114 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-N. Trochu, S. Mital, X.-p. Zhang, X. Xu, M. Ochoa, J. K Liao, F. A Recchia, and T. H Hintze Preservation of NO production by statins in the treatment of heart failure Cardiovasc Res, November 1, 2003; 60(2): 250 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Jones, Y. Teshima, M. Akao, and E. Marban Simvastatin Attenuates Oxidant-Induced Mitochondrial Dysfunction in Cardiac Myocytes Circ. Res., October 17, 2003; 93(8): 697 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Lee, J. S. Gounarides, E. S. Roos, and M. S. Wolin Influence of peroxynitrite on energy metabolism and cardiac function in a rat ischemia-reperfusion model Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1385 - H1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adler, E. Messina, B. Sherman, Z. Wang, H. Huang, A. Linke, and T. H. Hintze NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1015 - H1022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wunderlich, U. Flogel, A. Godecke, J. Heger, and J. Schrader Acute Inhibition of Myoglobin Impairs Contractility and Energy State of iNOS-Overexpressing Hearts Circ. Res., June 27, 2003; 92(12): 1352 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Godecke, A. Molojavyi, J. Heger, U. Flogel, Z. Ding, C. Jacoby, and J. Schrader Myoglobin Protects the Heart from Inducible Nitric-oxide Synthase (iNOS)-mediated Nitrosative Stress J. Biol. Chem., June 6, 2003; 278(24): 21761 - 21766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sato, H. Yaoita, K. Maehara, and Y. Maruyama Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H359 - H368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Z. Kojic, U. Flogel, J. Schrader, and U. K. M. Decking Endothelial NO formation does not control myocardial O2 consumption in mouse heart Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H392 - H397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Brutsaert Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity Physiol Rev, January 1, 2003; 83(1): 59 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Cotton, M T Kearney, and A M Shah Nitric oxide and myocardial function in heart failure: friend or foe? Heart, December 1, 2002; 88(6): 564 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Linke, W. Li, H. Huang, Z. Wang, and T. H. Hintze Role of cardiac eNOS expression during pregnancy in the coupling of myocardial oxygen consumption to cardiac work Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1208 - H1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Adler and H. Huang Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1788 - 1794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Park, S. E. Woodman, W. Schubert, A. W. Cohen, P. G. Frank, M. Chandra, J. Shirani, B. Razani, B. Tang, L. A. Jelicks, et al. Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype Am. J. Pathol., June 1, 2002; 160(6): 2207 - 2217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Sawyer and J. Loscalzo Myocardial Hibernation: Restorative or Preterminal Sleep? Circulation, April 2, 2002; 105(13): 1517 - 1519. [Full Text] [PDF]
|
|
|
|
|
|
L. Dai, P. S. Brookes, V. M. Darley-Usmar, and P. G. Anderson Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO{middle dot} Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2261 - H2269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P. Shannon Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2270 - H2281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Adler, H. Huang, J. N. Trochu, X. Xu, S. Gupta, and T. H. Hintze Simvastatin reverses impaired regulation of renal oxygen consumption in congestive heart failure Am J Physiol Renal Physiol, November 1, 2001; 281(5): F802 - F809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Setty, X. Bian, J. D. Tune, and H. F. Downey Endogenous nitric oxide modulates myocardial oxygen consumption in canine right ventricle Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H831 - H837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shen, R. Tian, K. W. Saupe, M. Spindler, and J. S. Ingwall Endogenous nitric oxide enhances coupling between O2 consumption and ATP synthesis in guinea pig hearts Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H838 - H846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Grieve, P. A. MacCarthy, N. P. Gall, A. C. Cave, and A. M. Shah Divergent Biological Actions of Coronary Endothelial Nitric Oxide During Progression of Cardiac Hypertrophy Hypertension, August 1, 2001; 38(2): 267 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Y. T. Hart, E. L. Hahn, D. M. Meyer, J. C. Burnett Jr., and M. M. Redfield Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H146 - H154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E Loke, E. J Messina, E. G Shesely, G. Kaley, and T. H Hintze Potential role of eNOS in the therapeutic control of myocardial oxygen consumption by ACE inhibitors and amlodipine Cardiovasc Res, January 1, 2001; 49(1): 86 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Flögel, M. W. Merx, A. Gödecke, U. K. M. Decking, and J. Schrader Myoglobin: A scavenger of bioactive NO PNAS, December 28, 2000; (2000) 11460298. [Abstract] [Full Text]
|
|
|
|
|
|
J.-N. Trochu, J.-B. Bouhour, G. Kaley, and T. H. Hintze Role of Endothelium-Derived Nitric Oxide in the Regulation of Cardiac Oxygen Metabolism : Implications in Health and Disease Circ. Res., December 8, 2000; 87(12): 1108 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Shen, P. S Buie, J. J Lynch, S. M Krause, and X.-L. Ma Chronic therapy with an ETA/B receptor antagonist in conscious dogs during progression of congestive heart failure: Intracellular Ca2+ regulation and nitric oxide mediated coronary relaxation Cardiovasc Res, November 1, 2000; 48(2): 332 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhao, X. Zhang, X. Xu, M. S. Wolin, and T. H. Hintze Depressed modulation of oxygen consumption by endogenous nitric oxide in cardiac muscle from diabetic dogs Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H520 - H527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Canty Jr. Nitric Oxide and Short-Term Hibernation : Friend or Foe? Circ. Res., July 21, 2000; 87(2): 85 - 87. [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, H. Post, M. C. Michel, M. Kelm, and R. Schulz Endogenous Nitric Oxide and Myocardial Adaptation to Ischemia Circ. Res., July 21, 2000; 87(2): 146 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Hare, R. A. Lofthouse, G. J. Juang, L. Colman, K. M. Ricker, B. Kim, H. Senzaki, S. Cao, R. S. Tunin, and D. A. Kass Contribution of Caveolin Protein Abundance to Augmented Nitric Oxide Signaling in Conscious Dogs With Pacing-Induced Heart Failure Circ. Res., May 26, 2000; 86(10): 1085 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shinke, H. Takaoka, M. Takeuchi, K. Hata, H. Kawai, H. Okubo, Y. Kijima, T. Murata, and M. Yokoyama Nitric Oxide Spares Myocardial Oxygen Consumption Through Attenuation of Contractile Response to {beta}-Adrenergic Stimulation in Patients With Idiopathic Dilated Cardiomyopathy Circulation, April 25, 2000; 101(16): 1925 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Leone Jr., P. M. Scholz, and H. R. Weiss Nitroprusside Attenuates Myocardial Stunning Through Reduced Contractile Delay and Time Experimental Biology and Medicine, March 1, 2000; 223(3): 263 - 269. [Abstract] [Full Text]
|
|
|
|
|
|
D. Sun, A. Huang, G. Zhao, R. Bernstein, P. Forfia, X. Xu, A. Koller, G. Kaley, and T. H. Hintze Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H461 - H468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shen, K. Asai, M. Uechi, M. A. Mathier, R. P. Shannon, S. F. Vatner, and J. S. Ingwall Progressive Loss of Myocardial ATP Due to a Loss of Total Purines During the Development of Heart Failure in Dogs : A Compensatory Role for the Parallel Loss of Creatine Circulation, November 16, 1999; 100(20): 2113 - 2118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shizukuda, A. Helisch, R. Yokota, and J. A. Ware Downregulation of Protein Kinase C{delta} Activity Enhances Endothelial Cell Adaptation to Hypoxia Circulation, November 2, 1999; 100(18): 1909 - 1916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Krieg, T. Wahlers, W. Giess, R. Rohde, M. Hartrumpf, M. Bund, and A. Haverich Inhaled nitric oxide and inhaled prostaglandin E1: effect on left ventricular contractility when used for treatment of experimental pulmonary hypertension Eur. J. Cardiothorac. Surg., November 1, 1999; 14(5): 494 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Recchia, P. I. McConnell, K. E. Loke, X. Xu, M. Ochoa, and T. H. Hintze Nitric oxide controls cardiac substrate utilization in the conscious dog Cardiovasc Res, November 1, 1999; 44(2): 325 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Loke, C. M. L. Curran, E. J. Messina, S. K. Laycock, E. G. Shesely, O. A. Carretero, and T. H. Hintze Role of Nitric Oxide in the Control of Cardiac Oxygen Consumption in B2-Kinin Receptor Knockout Mice Hypertension, October 1, 1999; 34(4): 563 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Loke, S. K. Laycock, S. Mital, M. S. Wolin, R. Bernstein, M. Oz, L. Addonizio, G. Kaley, and T. H. Hintze Nitric Oxide Modulates Mitochondrial Respiration in Failing Human Heart Circulation, September 21, 1999; 100(12): 1291 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Horimoto, A. E. Saltman, G. R. Gaudette, and I. B. Krukenkamp Nitric oxide-generating {beta}-adrenergic blocker nipradilol preserves postischemic cardiac function Ann. Thorac. Surg., September 1, 1999; 68(3): 844 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Drexler Nitric Oxide Synthases in the Failing Human Heart : A Doubled-Edged Sword? Circulation, June 15, 1999; 99(23): 2972 - 2975. [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Crystal, X. Zhou, A. A. Halim, S. Alam, M. El-Orbany, and M. R. Salem Nitric oxide does not modulate whole body oxygen consumption in anesthetized dogs J Appl Physiol, June 1, 1999; 86(6): 1944 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Forfia, X. Zhang, D. R. Knight, A. H. Smith, C. P. A. Doe, E. A. Wolfgang, D. M. Flynn, M. S. Wolin, and T. H. Hintze NO modulates myocardial O2 consumption in the nonhuman primate: an additional mechanism of action of amlodipine Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2069 - H2075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Matter, L. Mandinov, P. A. Kaufmann, G. Vassalli, Z. Jiang, and O. M. Hess Effect of NO Donors on LV Diastolic Function in Patients With Severe Pressure-Overload Hypertrophy Circulation, May 11, 1999; 99(18): 2396 - 2401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Han, Z. Ming, and W. W. Lautt Shear stress-induced nitric oxide antagonizes adenosine effects on intestinal metabolism Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1227 - G1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Loke, P. I. McConnell, J. M. Tuzman, E. G. Shesely, C. J. Smith, C. J. Stackpole, C. I. Thompson, G. Kaley, M. S. Wolin, and T. H. Hintze Endogenous Endothelial Nitric Oxide Synthase–Derived Nitric Oxide Is a Physiological Regulator of Myocardial Oxygen Consumption Circ. Res., April 16, 1999; 84(7): 840 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J Crystal and X. Zhou Nitric oxide does not modulate the increases in blood flow, O2 consumption, or contractility during CaCl2 administration in canine hearts Cardiovasc Res, April 1, 1999; 42(1): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kojda and K. Kottenberg Regulation of basal myocardial function by NO Cardiovasc Res, March 1, 1999; 41(3): 514 - 523. [Full Text] [PDF]
|
|
|
|
|
|
E. Clementi, G. C. Brown, N. Foxwell, and S. Moncada On the mechanism by which vascular endothelial cells regulate their oxygen consumption PNAS, February 16, 1999; 96(4): 1559 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Recchia, P. I. McConnell, R. D. Bernstein, T. R. Vogel, X. Xu, and T. H. Hintze Reduced Nitric Oxide Production and Altered Myocardial Metabolism During the Decompensation of Pacing-Induced Heart Failure in the Conscious Dog Circ. Res., November 16, 1998; 83(10): 969 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang Cardiac sympathetic afferent stimulation by bradykinin in heart failure: role of NO and prostaglandins Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H783 - H788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takano, S. Manchikalapudi, X.-L. Tang, Y. Qiu, A. Rizvi, A. K. Jadoon, Q. Zhang, and R. Bolli Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits Circulation, August 4, 1998; 98(5): 441 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Suto, A. Mikuniya, T. Okubo, H. Hanada, N. Shinozaki, and K. Okumura Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H41 - H49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Laycock, T. Vogel, P. R. Forfia, J. Tuzman, X. Xu, M. Ochoa, C. I. Thompson, A. Nasjletti, and T. H. Hintze Role of Nitric Oxide in the Control of Renal Oxygen Consumption and the Regulation of Chemical Work in the Kidney Circ. Res., June 29, 1998; 82(12): 1263 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Xie, P. M. Kaminski, and M. S. Wolin Inhibition of Rat Cardiac Muscle Contraction and Mitochondrial Respiration by Endogenous Peroxynitrite Formation During Posthypoxic Reoxygenation Circ. Res., May 4, 1998; 82(8): 891 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E Klabunde, J. Tse, and H. R Weiss Guanylyl cyclase inhibition reduces contractility and decreases cGMP and cAMP in isolated rat hearts Cardiovasc Res, March 1, 1998; 37(3): 676 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli, S. Manchikalapudi, X.-L. Tang, H. Takano, Y. Qiu, Y. Guo, Q. Zhang, and A. K. Jadoon The Protective Effect of Late Preconditioning Against Myocardial Stunning in Conscious Rabbits Is Mediated by Nitric Oxide Synthase : Evidence That Nitric Oxide Acts Both as a Trigger and as a Mediator of the Late Phase of Ischemic Preconditioning Circ. Res., December 19, 1997; 81(6): 1094 - 1107. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text]
|
|
|
|
|
|
U. Flogel, M. W. Merx, A. Godecke, U. K. M. Decking, and J. Schrader Myoglobin: A scavenger of bioactive NO PNAS, January 16, 2001; 98(2): 735 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Setty, J. D. Tune, and H. F. Downey Nitric oxide modulates right ventricular flow and oxygen consumption during norepinephrine infusion Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H696 - H703. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||