Published online before print May 6, 2004, doi: 10.1161/01.RES.0000131497.73744.1a
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© 2004 American Heart Association, Inc.
Integrative Physiology |
Flow-Dependent Dilation Mediated by Endogenous Kinins Requires Angiotensin AT2 Receptors
From the Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 541, Hôpital Lariboisière, Paris, France. Present address for R.H.P.H. is the Department of Pharmacology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands; for P.M., M.B.-F., F.A.-G. is INSERM Unit 367, Paris, France; and for T.I. is the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn.
Correspondence to Chantal M. Boulanger, PhD, INSERM Unit 541, Hôpital Lariboisière, 41 Bd de la Chapelle, F-75475 Paris Cedex 10, France. E-mail chantal.boulanger{at}larib.inserm.fr
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Abstract |
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The vascular kallikrein-kinin system contributes to about one third of flow-dependent dilation in mice carotid arteries, by activating bradykinin B2 receptors coupled to endothelial nitric oxide (NO) release. Because the bradykinin/NO pathway may mediate some of the effects of angiotensin II AT2 receptors, we examined the possible contribution of AT2 receptors to the kinin-dependent response to flow. Changes in outer diameter after increases in flow rate were evaluated in perfused arteries from wild-type animals (TK+/+) and in tissue kallikrein-deficient mice (TK–/–) in which the presence of AT2 receptor expression was verified. Saralasin, a nonselective angiotensin II receptor antagonist, impaired significantly flow-induced dilation in TK+/+, whereas it had no effect in TK–/– mice. In both groups, blockade of AT1 receptors with losartan or candesartan did not affect the response to flow. Inhibition of AT2 receptors with PD123319 reduced significantly flow-induced dilation in TK+/+ mice, but had no significant effect in TK–/– mice. Combining PD123319 with the bradykinin B2 receptor antagonist HOE-140 had no additional effect to AT2 receptor blockade alone in TK+/+ arteries. Flow-dependent-dilation was also impaired in AT2 receptor deficient mice (AT2–/–) when compared with wild-type littermates. Furthermore, HOE-140 significantly reduced the response to flow in the AT2+/+, but not in AT2–/– mice. In conclusion, this study demonstrates that the presence of functional AT2 receptors is necessary to observe the contribution of the vascular kinin-kallikrein system to flow-dependent dilation.
Key Words: kinins • angiotensin II • flow-dependent vasodilation • angiotensin AT2 receptor • bradykinin B2 receptor
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Introduction |
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Kallikreins are a distinct group of serine proteases, which are capable of generating vasoactive kinins from kininogen in vitro. Vascular tissue contains kininogen and kallikrein mRNA, suggesting the existence of an endogenous kallikrein-kinin system (KKS). Tissue KKS is present in both endothelial and smooth muscle cells of various vascular territories and is different from the circulating plasma kallikrein-kinin system.1–4 Indeed, tissue kallikrein (TK) is encoded by the kallikrein klk1 gene, and experimental evidence suggests that endogenously formed kinins could participate in the regulation of vascular tone.5–9 We recently showed that tissue kallikrein plays an essential role in kinins synthesis within the vascular wall of mice carotid arteries.10 In addition, this tissue KKS contributes to about one third of flow-induced dilation through activation of bradykinin B2 receptors leading to NO release in mouse carotid arteries.10 Flow-dependent dilation enables arteries to increase their diameter in response to changes in blood flow after the release of endothelial factors such as nitric oxide (NO) or prostacyclin to ensure appropriate organ perfusion.11–14 Flow-dependent dilation is a complex response involving not only local mediators (such as kinins) but also mechanical activation of endothelial cells, integrins, and cytoskeleton.14 Other peptide systems such as angiotensin II can also contribute to flow-dependent dilatation by activating AT2 receptors, as demonstrated in resistance arteries.15
Interestingly, several studies suggested a possible link between angiotensin II receptors and bradykinin B2 receptors regarding nitric oxide production.16–24 In vascular endothelial cells, the production of NO by angiotensin II is caused by activation of the angiotensin II type 2 (AT2) receptor.16 In addition, AT2 receptors stimulation by exogenous angiotensin II leads to an increase in cyclic GMP level, through a mechanism involving bradykinin B2 receptors and NO release.17–23 Furthermore, overexpression of AT2 receptors increases bradykinin production presumably by activating kininogenase(s).25 However, there is no information regarding a possible relation between AT2 and bradykinin B2 receptor pathways during flow-induced dilation. Therefore, the purpose of the present study is to determine whether or not angiotensin AT2 receptors contribute to flow-dependent dilation mediated by endogenously formed kinins using isolated carotid arteries from control mice and mice lacking the tissue kallikrein klk1 gene.
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Materials and Methods |
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Animal Groups
Littermate 12-week-old male wild-type (TK+/+) and tissue kallikrein null (TK–/–) mice were used as previously described.10,26 Twelve-week-old male AT2 receptor-deficient mice (AT2–/–) and their age-matched wild-type littermates (AT2+/+) were produced as described.27,28 They were backcrossed 10 times in the C57BL/6 genetic background.
RNA Extraction and RT-PCR Analysis
For each group of animals, carotid arteries from 10 mice were pooled and total RNA was extracted according to the Trizol reagent protocol (Life Technologies). The quality of the RNA preparation was confirmed by ethidium bromide staining.
The single-strand cDNA synthesis was performed in 20 µL of reaction buffer, consisting of first strand buffer 5x (GibcoBRL), RNase inhibitor (40 UI/µL), dinucleotide triphosphate (25 mmol/L), DTT (100 mmol/L) (Amersham), and Reverse MMLV (200 UI/µL). The reverse transcriptase reaction was performed by incubating the reaction mixture for 90 minutes at 37°C followed by 10 minutes at 65°C, using a 3' primer (5'-GGTTTTCCAAGGAAGGGGTATGAG). The polymerase chain reaction included three steps of denaturation (94°C, 45 seconds), annealing (65°C, 45 seconds), and extension (72°C, 105 seconds) for 35 cycles using the previously mentioned 3'-oligonucleotide and the other 5'-oligonucleotide (5'-CATGCTTTTGTTCTGGGCTTCGTC). These primers were taken from the unique exon from position 2176 to 2749 of the angiotensin II AT2 receptor gene, localized in chromosome X, thus, producing a 0.573-kb fragment of the AT2 receptor cDNA.29 The cDNA was amplified using 5 IU/µL of TaqDNA polymerase (Life Technologies) and 20 µmol/L of each set of primers in 50 µL of buffer 10x (22 mmol/L Tris-HCl; pH 8.4; 55 mmol/L KCl), MgCl2 (1.65 mmol/L), dinucleotide triphosphate (25 mmol/L) and 10 µL of loading dye (0.02% of red cresol and 60% of sucrose). The PRC products were sequenced and corresponded to the mouse AT2 receptor sequence.
In addition, expression of GAPDH was evaluated in parallel to that of AT2 receptor. Briefly, total RNA was reverse transcribed as mentioned above using the 3' primer (5'-CATGTAGGCCATGAGGTCCACCAC-3'). Then, the RT-product was amplified by 35 cycles as described for AT2 receptor, using the 3'-primer and the 5'-oligonucleotide (5'-TGAAGGTCGGTGTGAACGGATTTGGC-3'). The migration of both PCR products (AT2 receptor and GAPDH) was then followed by electrophoresis on a 2% agarose gel and ethidium bromide staining.
In Vitro Measurement of the Arterial Diameter
Carotid arteries were carefully exposed and quickly excised. The procedure was in accordance with the European Community guidelines on the care and use of laboratory animals (Ministère de l’Agriculture, France, authorization no 07430). They were cannulated at both extremities and then perfused continuously in vitro in a video-monitored perfusion system where flow and pressure can be modified independently, as previously described.10 Briefly, arteries were bathed in a physiological salt solution warmed (37°C) and gassed (95% O2/5% CO2) throughout the experiments. The pressure was monitored by a servoperfusion system. Intraluminal and extraluminal perfusions were provided by the mean of two perfusion pumps. The outer diameter, as well as proximal and distal pressures, was continuously recorded. The presence of the endothelium was ascertained by assessing the relaxation by acetylcholine (1 µmol/L) during phenylephrine-induced (1 µmol/L) contraction. Experiments were discarded when the relaxation by acetylcholine was smaller than 60% of that induced by sodium nitroprusside (0.1 mmol/L), because it indicated that the endothelial layer was damaged. At the end of each experiment, passive diameter was obtained after incubation of the artery (40 minutes) with a Ca2+-free control solution containing EGTA (2 mmol/L) and sodium nitroprusside (0.1 mmol/L), which abolished the smooth muscle tone. Phenylephrine and all the inhibitors or antagonists used in this study were delivered both in the intraluminal and extraluminal perfusions.
In Vitro Protocols for Mice Carotid Arteries
All experiments evaluating the response to increases in intraluminal flow rate were performed in presence of phenylephrine (1 µmol/L). When the contraction to phenylephrine was stable for at least 10 minutes, the intraluminal flow rate was increased in a stepwise manner from 10 to 800 µL/min. Each flow rate was applied for about 3 to 9 minutes, until the diameter reached a plateau, and then was augmented to the next level. Experiments were performed in the presence of either saralasin (a nonspecific AT1 and AT2 blocker; 1 µmol/L), losartan (an angiotensin AT1 antagonist; 0.1 µmol/L), candesartan (an angiotensin AT1 antagonist; 10 nmol/L), PD123319 (an angiotensin AT2 antagonist; 1 µmol/L), or HOE-140 (a bradykinin B2 receptor antagonist;1 µmol/L). Tissues were preincubated for 40 minutes with each antagonist or inhibitor in intraluminal and extraluminal perfusions. Unless otherwise indicated, responses under control conditions were obtained on contralateral carotid arteries.
Some experiments were performed on isolated mice mesenteric arteries, which were mounted as described above for carotid arteries. Mesenteric arteries basal diameters in AT2+/+ and AT2–/– mice were 177±12 (n=7) and 181±20 µm (n=6), respectively. The arteries were perfused (40 µL/min), pressurized (80 mm Hg), and dilatation to increasing concentrations of exogenous bradykinin (0.1 nmol/L to 10 µmol/L; given extraluminally) was recorded during contractions induced by the thromboxane analog U46619 (1 to 10 nmol/L).
Drugs and Chemical Agents
The compounds used for in vitro studies were acetylcholine chloride, bradykinin diacetate salt, L-phenylephrine hydrochloride, PD 123319, and losartan (Sigma). HOE-140 was kindly provided by Drs H.J. Lang and B.A. Schölkens (Hoechst-Marion-Roussel, Frankfurt, Germany). Candesartan was kindly provided by ASTRA-ZENECA.
Data Analysis and Statistics
Data are given as changes in diameter (microns) from the artery diameter obtained during contraction with phenylephrine. Results are expressed as mean±SEM of n experiments; n represents the number of animals used for each experimental protocol. pD2 values represent the negative logarithm of the concentration of agonist, which causes 50% of its maximal response. Statistical evaluation was performed by use of ANOVA for factorial or repeated measurements, followed by Scheffe t test.30 Values of P
0.05 were considered to be statistically significant.
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Vasoactive Responses in Perfused TK+/+ and TK–/– Mouse Carotid Arteries
Exposure of perfused TK+/+ and TK–/– carotid arteries to phenylephrine, acetylcholine, or sodium nitroprusside caused similar changes in outer diameter for each set of experiments (Table). Step-increases in intraluminal flow rate augmented the carotid artery diameter in both TK+/+ and TK–/– animals. At high flow rates, this response to flow was significantly smaller in preparations from TK–/– mice when compared with TK+/+ mice, as previously observed10 (P=0.0003) (Figure 1).
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; 
) or in the presence of saralasin (
; 
). *Significant difference when compared with control conditions (P
Effect of Angiotensin II Receptor Antagonists on Flow-Dependent Response
In TK+/+ mice, flow-dependent dilation was significantly impaired by the nonspecific angiotensin II receptors antagonist saralasin (P=0.02 between 200 and 800 µL/min) (Figure 1). Conversely, saralasin did not significantly modify the response to flow of TK–/– carotid arteries (P=0.84) (Figure 1). We then investigated the effect of preferential angiotensin AT1 and AT2 receptor antagonists on the response to flow. The response to flow was not affected by the AT1 receptor antagonist losartan, in both TK+/+ and TK–/– arteries (P=0.46 and P=0.71 respectively; Figure 2). The same conclusion was reached with candesartan (P=0.99 and P=0.66, respectively; data not shown).
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, n=6; 
, n=6). Control responses and experiments with losartan were performed on carotid arteries from the same mice, whereas experiments with losartan plus PD123319 were performed were obtained in a different set of animals. *Significant effect (PInterestingly, the AT2 receptor antagonist PD123319 significantly impaired the response to high flow rates in TK+/+ arteries exposed to losartan (P=0.05 when compared with losartan alone, and P=0.01 when compared with control conditions) (Figure 2). However, PD123319 had no significant effect on the response to flow in TK–/– arteries exposed to losartan (P=0.88, when compared with losartan alone, and P=0.74 when compared with control conditions) (Figure 2).
Expression of angiotensin II AT2 receptors was examined in carotid arteries of both TK+/+ and TK–/– mice by RT-PCR experiments. The AT2 receptor mRNA was present in carotid arteries of both groups, as demonstrated by the band at 0.6 kb (Figure 3).
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Effect of AT2 and B2 Receptors Antagonists on Flow-Dependent Response
In TK+/+ arteries, blockade of AT2 receptors with PD123319 alone reduced significantly flow-dependent dilation (P=0.005 from 200 to 800 µL/min). Interestingly, the response to flow of TK+/+ arteries exposed to PD123319 was not different from that of TK–/– arteries under control conditions (P=0.59) (Figure 4). Furthermore, PD123319 alone had no significant effect on the response to flow of TK–/– arteries (P=0.19) (Figure 4).
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The bradykinin B2 receptor antagonist HOE-140 also decreased the response to flow in TK+/+ arteries, as previously shown.10 Combining PD123319 plus HOE-140 significantly altered the response to flow when compared with control conditions (P=0.002 from 400 to 800 µL/min) (Figure 4). However, the impairment of flow-dependent dilation observed in the presence of PD123319 plus HOE-140 was not different from that caused by PD123319 alone (P=0.84).
Flow- and Bradykinin-Induced Dilation in AT2-Deficient Mice
Flow-dependent dilation was also significantly reduced in carotid arteries of AT2–/– mice when compared with their wild-type littermates AT2+/+ (P=0.04) (Figure 5). In addition, HOE-140 significantly decreased the response to flow in wild-type mice, but had no significant effect in the AT2–/– animals (P=0.01 and P=0.80, respectively) (Figure 5). Dilatation to exogenous bradykinin was investigated in perfused AT2+/+ and AT2–/– mesenteric arteries (n=6), where full dose-response curves to the peptide could be obtained. There was no significant difference in pD2 values (7.89±0.31 versus 8.18±0.33; P=0.54) and maximal responses (52±12 and 47±7%; P=0.63) to bradykinin between AT2+/+ and AT2–/– mesenteric arteries, respectively.
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Discussion |
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Tissue kallikrein activation contributes to one third of flow-mediated dilation by activating bradykinin B2 receptors coupled to endothelial NO synthesis.6–10,31 In this study, we demonstrate that the angiotensin AT2 receptor mediates the tissue-kallikrein-dependent dilation induced by flow in perfused murine carotid arteries.
Before investigating the possible contribution of AT2 receptors in flow-induced dilation mediated by the endogenous kinin-kallikrein system, we verified the presence of AT2 receptors in this preparation because these receptors are either absent or expressed at a low level in blood vessels from adult animals.32 RT-PCR experiments demonstrated the presence of angiotensin II AT2 receptor mRNA in arteries from control mice and from mice lacking tissue kallikrein (TK–/–). In perfused carotid arteries, we observed that the response to an increase in flow rate was significantly smaller in TK–/– when compared with TK+/+, thus confirming our previous study.10 The first hint regarding the involvement of angiotensin II receptors in flow-induced dilation mediated by endogenous kinins came from experiments with saralasin, a nonspecific angiotensin II AT1-AT2 receptor antagonist. Saralasin impaired the response to flow in TK+/+ arteries, but not in TK–/– arteries, which lack the formation of endogenous kinins.10,26
To determine further which of the angiotensin II receptor subtype is implicated in the response to flow mediated by the vascular kinin-kallikrein system, we investigated the effect on flow-induced dilation of preferential antagonists of either AT1 or AT2 receptors. Neither losartan nor candesartan modified flow-induced dilation in both TK+/+ and TK–/– animals, demonstrating that AT1 receptors do not contribute to the kinin-mediated dilation induced by flow. This interpretation is in agreement with other studies showing the lack of effect of angiotensin II AT1 receptor antagonists in flow-mediated dilation,15 but may contrast with previous studies showing that angiotensin II increases cyclic GMP levels by activating an endothelial AT1 receptor.33,34 The apparent discrepancy between these interpretations might result from the absence of flow rate and the use of high concentrations of exogenous angiotensin II in earlier studies.
Unlike the blockade of angiotensin AT1 receptor alone, exposing arteries to the combination of an AT1 and AT2 receptor antagonist decreased the response to flow in TK+/+ arteries, thus implying that angiotensin AT2 but not AT1 receptors contribute to flow-induced dilation in wild-type arteries. The inhibitory effects of PD123319 on flow-induced dilation in TK+/+ arteries further reinforce this interpretation. Interestingly, PD123319 reduced flow-induced dilation in wild-type mice to reach comparable levels to those observed in TK–/– mice under control conditions. The effect of AT1 and AT2 receptor antagonists was also examined in TK–/– arteries. Unlike TK+/+ arteries, blockade of AT1 and/or AT2 receptors did not modify the flow response in TK–/– arteries. As TK–/– arteries express both AT2 and B2 receptors,10 we can conclude from the present data that the participation of AT2 receptors to flow-induced dilation requires the presence of a functional vascular kallikrein-kinin system.
We further confirmed the results obtained with saralasin and the angiotensin AT2 receptor antagonist PD123319 in wild-type mice, by investigating the response to flow of carotid arteries obtained from AT2 receptor-deficient mice (AT2–/–).27 Flow-induced dilation was impaired in AT2–/– arteries, as compared with their wild-type littermates. In addition, the B2 receptor antagonist HOE-140 reduced the response to flow in AT2+/+ mice but not in AT2–/– mice, although deletion of AT2 receptor gene expression did not affect the functional response to B2 receptor activation with exogenous bradykinin. Taken together, these findings indicate that the participation of bradykinin B2 receptors to flow-induced dilation requires the presence of functional AT2 receptors.
Then, we investigated in wild-type mice the possible contribution of bradykinin B2 receptors to the AT2-dependent dilation in response to flow. The B2 receptor antagonist HOE-140 did not further decrease the response to flow in TK+/+ arteries already exposed to PD123319, although previous results demonstrated that in this strain, HOE-140 alone significantly impairs the response to flow under control conditions.10 Taken together, these results show that if bradykinin B2 receptors are blocked or if the vascular kinin-kallikrein system is inactivated, the AT2 receptor antagonist PD123319 no longer decreases the response to flow. Similarly, if AT2 receptors are blocked or not expressed, the bradykinin B2 receptor antagonist HOE-140 no longer inhibits flow-induced dilation. Thus, the present data demonstrate that the involvement of AT2 receptors in flow-dependent dilation requires the presence of both functional bradykinin B2 receptors and an active vascular kinin-kallikrein system. The present study also supports the conclusion that the part of flow-dependent dilation that is mediated by the local kinin-kallikrein system requires the presence of functional AT2 receptors. This interpretation is in agreement with previous studies indicating that AT2-dependent vasodilatation after exposure to exogenous angiotensin II involves bradykinin B2 receptor activation.17,20,23
Although the exact mechanism linking AT2 receptors and B2 receptors in flow-induced dilation remains to be elucidated, several hypotheses could be brought forward. The increase in flow rate may favor and augment the boundary layer mass transport of kinins and angiotensin II to their receptors, therefore decreasing their degradation rate.35,36 However, we cannot exclude the possibility that shear stress might also modulate endogenous peptides synthesis. Indeed, as a short-term increase in shear stress enhanced ACE activity, flow stimulation may augment the local production of angiotensin II.37 However, an increase in ACE activity would also contribute to a greater degradation of locally formed kinins,38 thus counterbalancing the effect of an augmented synthesis of angiotensin II. Interestingly, the lack of additional effect of the AT2 and the B2 receptor antagonists supports the conclusion that these two receptors do not act synergistically. This observation also favors the interpretation that these two receptor pathways lie upstream/downstream of each other. Activation of the angiotensin AT2 pathway might precede the stimulation of endogenous kinins synthesis and B2 receptors, as indicated from a recent study by Katada and Majima.23 This interpretation is also supported by data from this study and previous work10 as bradykinin response was unchanged after inactivation of either vascular kallikrein or AT2 receptors. Furthermore, overexpression of AT2 receptors in vascular smooth muscle cells increases intracellular acidosis, resulting in an increase in kininogenase activity and in turn the generation of kinins.25 However, activation of kininogenase(s) by lowering intracellular pH after AT2 receptor activation is not fully compatible with the known in vitro characteristics of tissue kallikrein activation.39 Alternatively, the present results may suggest a direct molecular interaction between B2 and AT2 receptors, comparable to the one recently described for AT1 and AT2,40 but these different hypotheses would require further investigations.
In conclusion, the present study demonstrates that in mice carotid arteries, the vascular kinin-kallikrein system contributes to one third of flow-induced dilation and requires the presence of both functional angiotensin AT2 and bradykinin B2 receptors.
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Acknowledgments |
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This study was supported by the Institut National de la Santé et de la Recherche Scientifique, the 6th European Framework Programme (contract no. LSHM-CT-2003-503254), the Ministère de la Recherche (ACI 2000-07), the Bristol Myers Squibb Institute for Medical Research, and the Groupe Paris-Nord de Recherche en Pathologie Vasculaire. S. Bergaya was supported by a fellowship from the Fondation pour la Recherche Médicale and R. Hilgers by a Marie Curie doctoral stipend from the European Community. We would also like to thank Eric Mathieu for his technical assistance.
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Footnotes |
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Presented in part at the 76th Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–13, 2003, and published in abstract form [Circulation. 2003;108(suppl. IV):IV–20.].
Original received January 22, 2003; resubmission received December 23, 2003; revised resubmission received April 1, 2004; accepted April 27, 2004.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
- Schmaier A, Kuo A, Lundberg D, Murray S, Cines D. The expression of high molecular weight kininogen in human umbilical vein endothelial cells. J Biol Chem. 1988; 263: 16327–16333.
[Abstract/Free Full Text] - Oza N, Schwartz J, Gould H, Levinsky N. Rat aortic smooth muscle cells in culture express kallikrein-kininogen and bradykinase activity. J Clin Invest. 1990; 85: 597–600.[Medline] [Order article via Infotrieve]
- Nolly H, Lama M, Carretero O, Scicli A. The kallikrein-kinin system in blood vessels. Agents Actions. 1992; 38 (suppl 3): 1–9.
- Yayama K, Hiroki S, Masaoki T, Hiroshi O. Expression of Low-Molecular-Weight Kininogen in mouse vascular smooth muscle cells. Biol Pharm Bull. 1998; 21: 772–774.[Medline] [Order article via Infotrieve]
- Wiemer G, Scholkens BA, Becker RH, Busse R. Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension. 1991; 18: 558–563.
[Abstract/Free Full Text] - Gardes J, Baussant T, Corvol P, Ménard J, Alhenc-Gelas F. Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II. Am J Physiol. 1990; 258: F1273–F1281.[Medline] [Order article via Infotrieve]
- Mombouli JV, Vanhoutte PM. Kinins mediate kallikrein-induced endothelium dependent relaxations in isolated canine coronary arteries. Biochem Biophys Res Comm. 1992; 185: 693–697.[CrossRef][Medline] [Order article via Infotrieve]
- Sakakibara T, Hintze TH, Nasjeletti A. Determinants of kinin release in isolated rat hindquarters. Am J Physiol. 1998; 43: R120–R125.
- Mombouli JV, Vanhoutte PM. Kinins and endothelium-dependent relaxations to converting enzyme inhibitors in perfused canine arteries. J Cardiovasc Pharm. 1991; 18: 926–927.[Medline] [Order article via Infotrieve]
- Bergaya S, Meneton P, Bloch-Faure M, Mathieu E, Alhenc-Gelas F, Levy BI, Boulanger CM. Decreased flow-dependent dilation in carotid arteries of tissue-kallikrein-knockout mice. Circ Res. 2001; 88: 593–599.
[Abstract/Free Full Text] - Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 1986; 8: 37–44.
[Abstract/Free Full Text] - Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986; 250: H1145–H1149.[Medline] [Order article via Infotrieve]
- Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995; 91: 1314–1319.
[Abstract/Free Full Text] - Davies P. Flow-mediated signal transduction in endothelial cells. In: JABevan, GKaley, GMRubanyi, eds. Flow-Dependent Regulation of Vascular Function. New York: Oxford University Press; 1995: 46–61.
- Matrougui K, Loufrani L, Heymes C, Levy B. I, Henrion D. Activation of AT2 receptors by endogenous angiotensin II is involved in flow-induced dilatation in rat resistance arteries. Hypertension. 1999; 34: 659–665.
[Abstract/Free Full Text] - Wiemer G, Scholkens B. A, Busse R, Wagner A, Heitsch H, Linz W. The functional role of angiotensin II subtype AT2-receptors in endothelial cells and isolated ischemic rat hearts. Pharm Pharmacol Lett. 1993; 3: 24–27.
- Seyedi N, Xu X, Nasjletti A, Hintze TH. Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension. 1995; 26: 164–170.
[Abstract/Free Full Text] - Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure: role of kinins and angiotensin II type 2 receptors. J Clin Invest. 1997; 99: 1926–1935.[Medline] [Order article via Infotrieve]
- Henrion D, Kubis N, Levy BI. Physiological and pathophysiological functions of the AT2 subtype receptor of angiotensin II. From large arteries to the microcirculation. Hypertension. 2001; 38: 1150–1157.
[Abstract/Free Full Text] - Gohlke P, Pees C, Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension. 1998; 31: 349–355.
[Abstract/Free Full Text] - Siragy HM, Inagami T, Ichiki T, Carey RM. Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A. 1999; 96: 6506–6510.
[Abstract/Free Full Text] - Tanaka M, Tsuchida S, Imai T, Fuji N, Miyazaki H, Ichiki T, Naruse M, Inagami T. Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice. Biochem Biophys Res Commun. 1999; 258: 194–198.[CrossRef][Medline] [Order article via Infotrieve]
- Katada J, Majima M. AT2 receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions. Br J Pharmacol. 2002; 136: 484–491.[CrossRef][Medline] [Order article via Infotrieve]
- Vanhoutte PM. Endothelial AT2-receptors: chicken or egg? Br J Pharmacol. 2002; 136: 481–483.[CrossRef][Medline] [Order article via Infotrieve]
- Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, Miyazaki M, Nozawa Y, Ozono R, Nakagawa K, Miwa T, Kawada N, Mori Y, Shibasaki Y, Tanaka Y, Fujiyama S, Koyama Y, Fujiyama A, Takahashi H, Iwasaka T. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest. 1999; 104: 925–935.[Medline] [Order article via Infotrieve]
- Meneton P, Bloch-Faure M, Hagege A, Ruetten H, Huang W, Bergaya S, Ceiler D, Gehring D, Martins I, Salmon G, Boulanger C. M, Nussberger J, Crozatier B, Gasc JM, Heudes D, Bruneval P, Doestchman M, Ménard J, Alhenc-Gelas F. Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice. Proc Natl Acad Sci U S A. 2001; 98: 2634–2639.
[Abstract/Free Full Text] - Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature. 1995; 377: 748–750.[CrossRef][Medline] [Order article via Infotrieve]
- Senbonmatsu T, Ichihara S, Price E, Gaffney F. A and Inagami T. Evidence for angiotensin type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest. 2000; 106: 81–85.[Medline] [Order article via Infotrieve]
- Nakajima M, Mukoyama M, Pratt RE, Horiuchi M, Dzau YJ. Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor. Biochem Biophys Res Commun. 1993; 197: 393–399.[CrossRef][Medline] [Order article via Infotrieve]
- Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res. 1980; 47: 1–9.
[Abstract/Free Full Text] - Groves P, Kurz S, Hanjürg J, Drexler H. Role of endogenous bradykinin in human coronary vasomotor control. Circulation. 1995; 92: 3424–3430.
[Abstract/Free Full Text] - Hutchinson HG, Hein L, Fujinaga M, Pratt RE. Modulation of vascular development and injury by angiotensin II. Cardiovasc Res. 1999; 41: 689–700.
[Abstract/Free Full Text] - Caputo L, Benessiano J, Boulanger CM, Levy BI. Angiotensin II increases cGMP content via endothelial angiotensin II AT1 subtype receptors in the rat carotid artery. Arterioscler Thromb Vasc Biol. 1995; 15: 1646–1651.
[Abstract/Free Full Text] - Boulanger CM, Caputo L, Levy BI. Endothelial AT1-mediated release of nitric oxide decreases angiotensin II contractions in rat carotid artery. Hypertension. 1995; 26: 752–757.
[Abstract/Free Full Text] - Dull RO, Davies PF. Flow modulation of agonist (ATP) response (Ca2+) coupling in vascular endothelial cells. Am J Physiol. 1991; 261: H149–H156.[Medline] [Order article via Infotrieve]
- Mo M, Eskin SG, Schilling WP. Flow-induced changes in Ca2+ signaling of vascular endothelial cells: effects of shear stress and ATP. Am J Physiol. 1991; 260: H1698–H1707.[Medline] [Order article via Infotrieve]
- Rieder MJ, Carmona R, Krieger JE, Pritchard KA Jr., Greene AS. Suppression of angiotensin-converting enzyme expression and activity by shear stress. Circ Res. 1997; 80: 312–319.
[Abstract/Free Full Text] - Kramer HJ. The renal kallikrein-kinin system. Renal Physiol. 1979; 80: 107–121.
- Rabinovich SE, Lobareva LS, Paskhina TS. Purification and some physico-chemical and enzymatic properties of tissue kallikrein from human urine. Biokhimiia. 1990; 55: 1675–1689.[Medline] [Order article via Infotrieve]
- AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U. The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem. 2001; 276: 39721–39726.
[Abstract/Free Full Text]
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