Nitric oxide modulates myocardial oxygen consumption in the failing heart.

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 (MVO2). 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 MVO2 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 MVO2 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 MVO2 at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between MVO2 and rate-pressure product. In contrast, S-methylisothiourea had no effect on MVO2 or coronary flow in normal animals, although nonselective NOS inhibition with N(G)-nitro-L-arginine did cause an increase of MVO2 in normal and in CHF animals.

CONCLUSIONS

The results indicate that endogenous NO can modulate MVO2 in failing hearts, but unlike the normal heart, this NO appears to be produced, at least in part, by iNOS.