Published Online
on June 17, 2002

A more recent version of this article appeared on July 9, 2002

This Article Full Text (PDF) All Versions of this Article: 106/2/273    most recent 01.CIR.0000021120.90970.B9v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Bache, R. J. Search for Related Content PubMed Articles by Chen, Y. Articles by Bache, R. J. Related Collections Biochemistry and metabolism Energy metabolism

Submitted on March 5, 2002
Revised on April 22, 2002
Accepted on April 24, 2002

Nitric Oxide Modulates Myocardial Oxygen Consumption in the Failing Heart

YingJie Chen MD, PhD, Jay H. Traverse MD, Ruisheng Du PhD, MingXiao Hou MD, PhD, and Robert J. Bache MD^*

From the Department of Medicine, Division of Cardiology, University of Minnesota Medical School, Minneapolis.

^* To whom correspondence should be addressed. E-mail: bache001{at}tc.umn.edu.

Background—Endogenous nitric oxide (NO) has been reported to inhibit oxygen consumption in the normal heart, so that nonselective inhibition of NO synthase (NOS) caused an increase of myocardial oxygen consumption (MV^·O₂). Although endothelial NOS responses are depressed in congestive heart failure (CHF), inducible NOS (iNOS) may be expressed in failing myocardium.

Methods and Results—This study tested the hypothesis that NOS inhibition would increase MV^·O₂ in the failing heart. CHF was produced in dogs by use of the rapid ventricular pacing model. In comparison with normal values, animals with CHF had reduced coronary blood flow and MV^·O₂ at rest, with a blunted response to treadmill exercise. Selective iNOS inhibition with S-methylisothiourea (1.5 mg/kg IC) increased left ventricular systolic pressure and left ventricular dP/dt and caused an increase in MV^·O₂ at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between MV^·O₂ and rate-pressure product. In contrast, S-methylisothiourea had no effect on MV^·O₂ or coronary flow in normal animals, although nonselective NOS inhibition with N^G-nitro-L-arginine did cause an increase of MV^·O₂ in normal and in CHF animals.

Conclusions—The results indicate that endogenous NO can modulate MV^·O₂ in failing hearts, but unlike the normal heart, this NO appears to be produced, at least in part, by iNOS.

Key words: metabolism • myocardium • blood flow • nitric oxide

This article has been cited by other articles:

				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]

				P. Zhang, X. Xu, X. Hu, E. D. van Deel, G. Zhu, and Y. Chen Inducible Nitric Oxide Synthase Deficiency Protects the Heart From Systolic Overload-Induced Ventricular Hypertrophy and Congestive Heart Failure Circ. Res., April 13, 2007; 100(7): 1089 - 1098. [Abstract] [Full Text] [PDF]

				M. Shibata, K. Qin, S. Ichioka, and A. Kamiya Vascular wall energetics in arterioles during nitric oxide-dependent and -independent vasodilation J Appl Physiol, June 1, 2006; 100(6): 1793 - 1798. [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]

				M. Shibata, S. Ichioka, and A. Kamiya Nitric oxide modulates oxygen consumption by arteriolar walls in rat skeletal muscle Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2673 - H2679. [Abstract] [Full Text] [PDF]

				Y. Chen, Y. Li, P. Zhang, J. H. Traverse, M. Hou, X. Xu, M. Kimoto, and R. J. Bache Dimethylarginine dimethylaminohydrolase and endothelial dysfunction in failing hearts Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2212 - H2219. [Abstract] [Full Text] [PDF]

				Y. Chen, M. Hou, Y. Li, J. H. Traverse, P. Zhang, D. Salvemini, T. Fukai, and R. J. Bache Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H133 - H141. [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]

				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]

				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]

				J. Zhang, Z. Chen, F. R. Cobb, and J. S. Stamler Role of Mitochondrial Aldehyde Dehydrogenase in Nitroglycerin-Induced Vasodilation of Coronary and Systemic Vessels: An Intact Canine Model Circulation, August 10, 2004; 110(6): 750 - 755. [Abstract] [Full Text] [PDF]

				D. A. Wink, K. M. Miranda, T. Katori, D. Mancardi, D. D. Thomas, L. Ridnour, M. G. Espey, M. Feelisch, C. A. Colton, J. M. Fukuto, et al. Orthogonal properties of the redox siblings nitroxyl and nitric oxide in the cardiovascular system: a novel redox paradigm Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2264 - H2276. [Abstract] [Full Text] [PDF]

				P. P. A. Mammen, S. B. Kanatous, I. S. Yuhanna, P. W. Shaul, M. G. Garry, R. S. Balaban, and D. J. Garry Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2132 - H2141. [Abstract] [Full Text] [PDF]

				P.B. Massion, O. Feron, C. Dessy, and J.-L. Balligand Nitric Oxide and Cardiac Function: Ten Years After, and Continuing Circ. Res., September 5, 2003; 93(5): 388 - 398. [Abstract] [Full Text] [PDF]

				H. Kogler, H. Fraser, S. McCune, R. Altschuld, and E. Marban Disproportionate enhancement of myocardial contractility by the xanthine oxidase inhibitor oxypurinol in failing rat myocardium Cardiovasc Res, September 1, 2003; 59(3): 582 - 592. [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]

				N. Paolocci, T. Katori, H. C. Champion, M. E. St. John, K. M. Miranda, J. M. Fukuto, D. A. Wink, and D. A. Kass From the Cover: Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: Independence from beta -adrenergic signaling PNAS, April 29, 2003; 100(9): 5537 - 5542. [Abstract] [Full Text] [PDF]