(Circulation. 1997;95:1328-1334.)
© 1997 American Heart Association, Inc.
Articles |
Blockade of Nitric Oxide Synthesis Reduces Myocardial Oxygen Consumption In Vivo
the Feinberg Cardiovascular Research Institute (A.J.S., C.A.D., F.J.K., K.R.H., G.S., A.D.Y., D.A.Q., K.A.A., J.J.J.) and the Departments of Medicine (F.J.K., G.S., A.S.Y.) and Surgery (A.J.S., C.A.D.), Northwestern University Medical School, Chicago, Ill.
Correspondence to Francis J. Klocke, MD, Feinberg Cardiovascular Research Institute, Tarry 12-703 (T233), Northwestern University Medical School, 303 E Chicago Ave, Chicago, IL 60611-3008. E-mail f-klocke{at}nwu.edu
Background Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O2 consumption and contractile performance remain unclear.
Methods and Results The effects of blockade of NO synthase were determined in intact dogs. Myocardial O2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N
-nitro-L-arginine methyl ester (L-NAME) or N-nitro-L-arginine. Decreases after doses of 1 and 10 mg/kg L-NAME averaged 23±3.8% and 34±7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductions occurred after the administration of L-NAME and N-nitro-L-arginine in chronically instrumented animals and were unaffected by ß-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O2 consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure.
Conclusions The blockade of NO synthesis reduces myocardial O2 consumption in vivo. The decrease in O2 consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by ß-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.
Key Words: nitric oxide • myocardial contraction • myocardium • oxygen • physiology
This article has been cited by other articles:
 |
|
 |
|
  M. Seddon, A. M. Shah, and B. Casadei Cardiomyocytes as effectors of nitric oxide signalling Cardiovasc Res, July 15, 2007; 75(2): 315 - 326. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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. Merkus, D. B. Haitsma, T.-Y. Fung, Y. J. Assen, P. D. Verdouw, and D. J. Duncker Coronary blood flow regulation in exercising swine involves parallel rather than redundant vasodilator pathways Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H424 - H433. [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]
|
|
|
|
 |
|
 Y. Chen, J. H. Traverse, R. Du, M. Hou, and R. J. Bache Nitric Oxide Modulates Myocardial Oxygen Consumption in the Failing Heart Circulation, July 9, 2002; 106(2): 273 - 279. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. Stumpe, U. K. M. Decking, and J. Schrader Nitric oxide reduces energy supply by direct action on the respiratory chain in isolated cardiomyocytes Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2350 - H2356. [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]
|
|
|
|
|
|
Y. Chen, R. Du, J. H. Traverse, and R. J. Bache Effect of sildenafil on coronary active and reactive hyperemia Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2319 - H2325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Duncker, R. Stubenitsky, P. A.L. Tonino, and P. D. Verdouw Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O2-consumption in exercising swine Cardiovasc Res, September 1, 2000; 47(4): 738 - 748. [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]
|
|
|
|
|
|
R. K. Kudej, S.-J. Kim, Y.-T. Shen, J. B. Jackson, A. B. Kudej, G.-P. Yang, S. P. Bishop, and S. F. Vatner Nitric oxide, an important regulator of perfusion-contraction matching in conscious pigs Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H451 - H456. [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]
|
|
|
|
|
|
T. Yada, O. Hiramatsu, H. Tachibana, E. Toyota, and F. Kajiya Role of NO and K+ATP channels in adenosine-induced vasodilation on in vivo canine subendocardial arterioles Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1931 - H1939. [Abstract] [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]
|
|
|
|
|
|
M. A. Gaballa, T. E. Raya, C. A. Hoover, and S. Goldman Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction Cardiovasc Res, June 1, 1999; 42(3): 627 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Meldrum Tumor necrosis factor in the heart Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R577 - R595. [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]
|
|