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 (MV̇O2). 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 MV̇O2 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 MV̇O2 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 MV̇O2 at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between MV̇O2 and rat-pressure product. In contrast, S-methylisothiourea had no effect on MV̇O2 or coronary flow in normal animals, although nonselective NOS inhibition with NG-nitro-L-arginine did cause an increase of MV̇O2 in normal and in CHF animals. Conclusions - The results indicate that endogenous NO can modulate MV̇O2 in failing hearts, but unlike the normal heart, this NO appears to be produced, at least in part, by iNOS.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jul 9 2002|
- Blood flow
- Nitric oxide