ROLE OF NITRIC-OXIDE IN CARDIAC BETA-ADRENOCEPTOR-INOTROPIC RESPONSE

We examined some of the signalling events in the negative modulation o f isoproterenol-induced stimulation of contractility in rat isolated a tria. Isoproterenol-mediated positive inotropic response is accompanie d by the stimulation of nitric oxide synthase (NOS) and an increase in the production of cyclic GMP (cGMP). Inhibition of NOS and guanylate cyclase increased the dose-response curve of isoproterenol on contract ility. Inhibitors of calcium flux or calcium calmodulin, but not of pr otein kinase C, abrogated these mechanisms. The existence of a modulat ory negative inotropic-cyclic GMP-mediated mechanism limiting the effe ct of beta-adrenergic stimulation in myocardium is discussed. (C) 1998 Elsevier Science Inc.