Positive inotropic effect of nitric oxide in myocardium.
Cardiac endothelium modulates underlying cardiac muscle performance probably by releasing certain regulatory factors. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cyclic GMP (cGMP), may be involved in this cardiac modulation. Many recent studies have examined inotropic effects of NO utilizing NO donors and NO-synthase inhibitors, both in vitro and in vivo, with apparently contradictory results. We examined the myocardial effects of NO-releasing nitrovasodilators (sodium nitroprusside (SNP), SIN-1 and S-nitrosoacetyl penicillamine (SNAP)), a cGMP analogue, 8-bromo-cGMP, and the cGMP phosphodiesterase inhibitor zaprinast, in isolated cat papillary muscle. A novel concentration-dependent positive inotropic effect of SNP and SIN-1 in muscles with damaged endocardial endothelium (EE) was observed which contrasted to their negative inotropic effect in muscles with intact EE. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. Concentration response curves with addition of SNAP and 8-bromo-cGMP resulted in a biphasic inotropic response. While administration of low concentrations of SNAP and 8-bromo cGMP induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Administration of zaprinast caused a monophasic concentration-dependent positive inotropic effect. We conclude that basal release of NO and consequent modest (physiological?) elevation in cGMP may preserve myocardial function, while large (pathological?) increases would depress myocardial function.
Department of Physiology and Medicine, University of Antwerp (RUCA), Belgium.
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P
Mohan
S U
SU
Sys
D L
DL
Brutsaert
D000818:Animals; D002415:Cats; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004699:Endocardium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP