Nitric oxide modulates myocardial oxygen consumption in the failing heart

Article

关键词: TUMOR-NECROSIS-FACTOR;    CONTRACTILE RESPONSE;    SKELETAL-MUSCLE;    BLOOD-FLOW;    SYNTHASE;    INHIBITION;    VASODILATION;    EXPRESSION;    FAILURE;    ENZYME;   

DOI  :  10.1161/01.CIR.0000021120.90970.B9

来源: SCIE

【 摘 要 】

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 (M(V)over dotO(2)). 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 M(V)over dotO(2) 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 M(V)over dotO(2) 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 M(V)over dotO(2) at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between M(V)over dotO(2) and rate-pressure product. In contrast, S-methylisothiourea had no effect on M(V)over dotO(2) or coronary flow in normal animals, although nonselective NOS inhibition with N-nitro-L-arginine did cause an increase Of M(V)over dotO(2) in normal and in CHF animals. Conclusions-The results indicate that endogenous NO can modulate M(V)over dotO(2) in failing hearts, but unlike the normal heart, this NO appears to be produced, at least in part, by iNOS.

【 授权许可】

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