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(Circulation. 2002;106:273.)
© 2002 American Heart Association, Inc.

Basic Science Reports

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; Robert J. Bache, MD

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

Correspondence to Robert J. Bache, MD, Department of Medicine, University of Minnesota Medical School, Mayo Mail Code 508, 420 Delaware St SE, Minneapolis, MN 55455. 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 (MO₂). 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 MO₂ 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 MO₂ 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 MO₂ at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between MO₂ and rate-pressure product. In contrast, S-methylisothiourea had no effect on MO₂ or coronary flow in normal animals, although nonselective NOS inhibition with N^G-nitro-L-arginine did cause an increase of MO₂ in normal and in CHF animals.

Conclusions— The results indicate that endogenous NO can modulate MO₂ 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

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