© 1999 American Heart Association, Inc.
Rapid Communication |
Endogenous Endothelial Nitric Oxide Synthase–Derived Nitric Oxide Is a Physiological Regulator of Myocardial Oxygen Consumption
From the Departments of Physiology (K.E.L., P.I.M., J.M.T., C.I.T., G.K., M.S.W., T.H.H.) and Pathology (C.J. Smith, C.J. Stackpole), New York Medical College, Valhalla, NY; Division of Hypertension and Vascular Research (E.G.S.), Henry Ford Hospital, Detroit, Mich.
Correspondence to Thomas H. Hintze, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Thomas_Hintze{at}nymc.edu
Abstract—Our objective was to determine the precise role of endothelial nitric oxide synthase (eNOS) as a modulator of cardiac O2 consumption and to further examine the role of nitric oxide (NO) in the control of mitochondrial respiration. Left ventricle O2 consumption in mice with defects in the expression of eNOS [eNOS (-/-)] and inducible NOS [iNOS (-/-)] was measured with a Clark-type O2 electrode. The rate of decreases in O2 concentration was expressed as a percentage of the baseline. Baseline O2 consumption was not significantly different between groups of mice. Bradykinin (10-4 mol/L) induced significant decreases in O2 consumption in tissues taken from iNOS (-/-) (-28±4%), wild-type eNOS (+/+) (-22±4%), and heterozygous eNOS(+/-) (-22±5%) but not homozygous eNOS (-/-) (-3±4%) mice. Responses to bradykinin in iNOS (-/-) and both wild-type and heterozygous eNOS mice were attenuated after NOS blockade with N-nitro-L-arginine methyl ester (L-NAME) (-2±5%, -3±2%, and -6±5%, respectively, P<0.05). In contrast, S-nitroso-N-acetyl-penicillamine (SNAP, 10-4 mol/L), which releases NO spontaneously, induced decreases in myocardial O2 consumption in all groups of mice, and such responses were not affected by L-NAME. In addition, pretreatment with bacterial endotoxin elicited a reduction in basal O2 consumption in tissues taken from normal but not iNOS (-/-)–deficient mice. Our results indicate that the pivotal role of eNOS in the control of myocardial O2 consumption and modulation of mitochondrial respiration by NO may have an important role in pathological conditions such as endotoxemia in which the production of NO is altered.
Key Words: endothelial nitric oxide synthase–derived nitric oxide • cardiac oxygen consumption
This article has been cited by other articles:
 |
|
 |
|
  M. Sonmez, F Narin, D Akkus, and S Ozdamar Effect of melatonin and vitamin C on expression of endothelial NOS in heart of chronic alcoholic rats Toxicology and Industrial Health, July 1, 2009; 25(6): 385 - 393. [Abstract] [PDF]
|
|
|
|
 |
|
 V. M. Victor, C. Nunez, P. D'Ocon, C. T. Taylor, J. V. Esplugues, and S. Moncada Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide Circ. Res., May 22, 2009; 104(10): 1178 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, B. Liu, J. L. Zweier, and G. He Formation of Hydrogen Peroxide and Reduction of Peroxynitrite via Dismutation of Superoxide at Reperfusion Enhances Myocardial Blood Flow and Oxygen Consumption in Postischemic Mouse Heart J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 402 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Erusalimsky and S. Moncada Nitric Oxide and Mitochondrial Signaling: From Physiology to Pathophysiology Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2524 - 2531. [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]
|
|
|
|
 |
|
 G. C. Brown and V. Borutaite Nitric oxide and mitochondrial respiration in the heart Cardiovasc Res, July 15, 2007; 75(2): 283 - 290. [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]
|
|
|
|
|
|
C. Martin, R. Schulz, H. Post, K. Boengler, M. Kelm, P. Kleinbongard, P. Gres, A. Skyschally, I. Konietzka, and G. Heusch Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia Cardiovasc Res, April 1, 2007; 74(1): 46 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Han, Y.-R. Chen, C. I. Jones III, G. Meenakshisundaram, J. L. Zweier, and B. R. Alevriadou Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1103 - C1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Bell, J. E. Clark, D. J. Hearse, and M. J. Shattock Reperfusion kinase phosphorylation is essential but not sufficient in the mediation of pharmacological preconditioning: Characterisation in the bi-phasic profile of early and late protection Cardiovasc Res, January 1, 2007; 73(1): 153 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Davidson and M. R. Duchen Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance Cardiovasc Res, July 1, 2006; 71(1): 10 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V. Cuong, N. Kim, J. B. Youm, H. Joo, M. Warda, J.-W. Lee, W. S. Park, T. Kim, S. Kang, H. Kim, et al. Nitric oxide-cGMP-protein kinase G signaling pathway induces anoxic preconditioning through activation of ATP-sensitive K+ channels in rat hearts Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1808 - H1817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Monnet, B. Ghaleh, L. Lucats, P. Colin, R. Zini, L. Hittinger, and A. Berdeaux Phenotypic adaptation of the late preconditioned heart: Myocardial oxygen consumption is reduced Cardiovasc Res, May 1, 2006; 70(2): 391 - 398. [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]
|
|
|
|
|
|
C. Ojaimi, W. Li, S. Kinugawa, H. Post, A. Csiszar, P. Pacher, G. Kaley, and T. H. Hintze Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1399 - H1407. [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]
|
|
|
|
 |
|
 X. Zhao, G. He, Y.-R. Chen, R. P. Pandian, P. Kuppusamy, and J. L. Zweier Endothelium-Derived Nitric Oxide Regulates Postischemic Myocardial Oxygenation and Oxygen Consumption by Modulation of Mitochondrial Electron Transport Circulation, June 7, 2005; 111(22): 2966 - 2972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Becker, A. Adler, A. Schneeberger, H. Huang, Z. Wang, E. Walsh, A. Koller, and T. H. Hintze Hyperhomocysteinemia, a Cardiac Metabolic Disease: Role of Nitric Oxide and the p22phox Subunit of NADPH Oxidase Circulation, April 26, 2005; 111(16): 2112 - 2118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinugawa, Z. Wang, P. M. Kaminski, M. S. Wolin, J. G. Edwards, G. Kaley, and T. H. Hintze Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene-Knockout Mice: Roles of Superoxide Anion and Nitric Oxide Circulation, March 29, 2005; 111(12): 1480 - 1486. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. Ilangovan, S. Osinbowale, A. Bratasz, M. Bonar, A. J. Cardounel, J. L. Zweier, and P. Kuppusamy Heat shock regulates the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1472 - C1481. [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]
|
|
|
|
|
|
A. Adler, H. Huang, Z. Wang, J. Conetta, E. Levee, X. Zhang, and T. H. Hintze Endocardial endothelium in the avascular frog heart: role for diffusion of NO in control of cardiac O2 consumption Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H14 - H21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gao, J. Chen, S. V. Brodsky, H. Huang, S. Adler, J. H. Lee, N. Dhadwal, L. Cohen-Gould, S. S. Gross, and M. S. Goligorsky Docking of Endothelial Nitric Oxide Synthase (eNOS) to the Mitochondrial Outer Membrane: A PENTABASIC AMINO ACID SEQUENCE IN THE AUTOINHIBITORY DOMAIN OF eNOS TARGETS A PROTEINASE K-CLEAVABLE PEPTIDE ON THE CYTOPLASMIC FACE OF MITOCHONDRIA J. Biol. Chem., April 16, 2004; 279(16): 15968 - 15974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kanai and J. Peterson Function and regulation of mitochondrially produced nitric oxide in cardiomyocytes Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H11 - H12. [Full Text] [PDF]
|
|
|
|
|
|
W. Li, T. Jue, J. Edwards, X. Wang, and T. H. Hintze Changes in NO bioavailabilty regulate cardiac O2 consumption: control by intramitochondrial SOD2 and intracellular myoglobin Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H47 - H54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brunner and G. Wolkart Peroxynitrite-induced cardiac depression: role of myofilament desensitization and cGMP pathway Cardiovasc Res, November 1, 2003; 60(2): 355 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Post, C. d'Agostino, V. Lionetti, M. Castellari, E. Y Kang, M. Altarejos, X. Xu, T. H Hintze, and F. A Recchia Reduced Left Ventricular Compliance and Mechanical Efficiency after Prolonged Inhibition of NO Synthesis in Conscious Dogs J. Physiol., October 1, 2003; 552(1): 233 - 239. [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]
|
|
|
|
 |
|
 J. B. Wittenberg and B. A. Wittenberg Myoglobin function reassessed J. Exp. Biol., June 15, 2003; 206(12): 2011 - 2020. [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]
|
|
|
|
|
|
F. Brunner, R. Maier, P. Andrew, G. Wolkart, R. Zechner, and B. Mayer Attenuation of myocardial ischemia/reperfusion injury in mice with myocyte-specific overexpression of endothelial nitric oxide synthase Cardiovasc Res, January 1, 2003; 57(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kaye, M. M. Parnell, and B. A. Ahlers Reduced Myocardial and Systemic L-Arginine Uptake in Heart Failure Circ. Res., December 13, 2002; 91(12): 1198 - 1203. [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]
|
|
|
|
|
|
U. Landmesser and H. Drexler Allopurinol and Endothelial Function in Heart Failure: Future or Fantasy? Circulation, July 9, 2002; 106(2): 173 - 175. [Full Text] [PDF]
|
|
|
|
|
|
A. Csiszar, Z. Ungvari, J. G. Edwards, P. Kaminski, M. S. Wolin, A. Koller, and G. Kaley Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function Circ. Res., June 14, 2002; 90(11): 1159 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Traverse, Y. Chen, M. Hou, and R. J. Bache Inhibition of NO production increases myocardial blood flow and oxygen consumption in congestive heart failure Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2278 - H2283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Recchia, J. C. Osorio, M. P. Chandler, X. Xu, A. R. Panchal, G. D. Lopaschuk, T. H. Hintze, and W. C. Stanley Reduced synthesis of NO causes marked alterations in myocardial substrate metabolism in conscious dogs Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E197 - E206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Borutaite, A. Matthias, H. Harris, S. Moncada, and G. C. Brown Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2256 - H2260. [Abstract] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R D Rakhit and M S Marber Nitric oxide: an emerging role in cardioprotection? Heart, October 1, 2001; 86(4): 368 - 372. [Full Text] [PDF]
|
|
|
|
|
|
U. K.M. Decking, J. P. Williams, R. Dahmann, T. Stumpe, M. Kelm, and J. Schrader The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase Cardiovasc Res, August 1, 2001; 51(2): 313 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Rakhit, M. H. Mojet, M. S. Marber, and M. R. Duchen Mitochondria as Targets for Nitric Oxide-Induced Protection During Simulated Ischemia and Reoxygenation in Isolated Neonatal Cardiomyocytes Circulation, May 29, 2001; 103(21): 2617 - 2623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adler, H. Huang, K. E. Loke, X. Xu, H. Tada, A. Laumas, and T. H. Hintze Endothelial nitric oxide synthase plays an essential role in regulation of renal oxygen consumption by NO Am J Physiol Renal Physiol, May 1, 2001; 280(5): F838 - F843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takeuchi, Y. Kihara, K. Inagaki, T. Yoneda, and S. Sasayama Endothelin-1 Has a Unique Oxygen-Saving Effect by Increasing Contractile Efficiency in the Isolated Rat Heart Circulation, March 20, 2001; 103(11): 1557 - 1563. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. Mital, K. E. Loke, L. J. Addonizio, M. C. Oz, and T. H. Hintze Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1897 - 1902. [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]
|
|
|
|
|
|
N. Paolocci, U. E. G. Ekelund, T. Isoda, M. Ozaki, K. Vandegaer, D. Georgakopoulos, R. W. Harrison, D. A. Kass, and J. M. Hare cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1982 - H1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kanno, P. C. Lee, Y. Zhang, C. Ho, B. P. Griffith, L. L. Shears II, and T. R. Billiar Attenuation of Myocardial Ischemia/Reperfusion Injury by Superinduction of Inducible Nitric Oxide Synthase Circulation, June 13, 2000; 101(23): 2742 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. y Schnitzler, C. Derst, J. Daut, and R. Preisig-Muller ATP-sensitive potassium channels in capillaries isolated from guinea-pig heart J. Physiol., June 1, 2000; 525(2): 307 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Goligorsky Making Sense out of Oxygen Sensor Circ. Res., April 28, 2000; 86(8): 824 - 826. [Full Text] [PDF]
|
|
|
|
|
|
R. D. Rakhit, R. J. Edwards, J. W. Mockridge, A. R. Baydoun, A. W. Wyatt, G. E. Mann, and M. S. Marber Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1211 - H1217. [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]
|
|
|
|
|
|
H. Tada, C. I. Thompson, F. A. Recchia, K. E. Loke, M. Ochoa, C. J. Smith, E. G. Shesely, G. Kaley, and T. H. Hintze Myocardial Glucose Uptake Is Regulated by Nitric Oxide via Endothelial Nitric Oxide Synthase in Langendorff Mouse Heart Circ. Res., February 18, 2000; 86(3): 270 - 274. [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]
|
|
|
|
 |
|
 C. J. Lowenstein NO news is good news PNAS, September 28, 1999; 96(20): 10953 - 10954. [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]
|
|