Role of nitric oxide and cGMP in cardiac B-adrenoceptor inotropic response.

L STERIN-BORDA; A GENARO; C PEREZ LEIROS; GA CREMASCHI; VILA-ECHAGUE; E BORDA

CELLULAR SIGNALLING

Elsevier Science Ltd.

Lugar: England; Año: 1998 vol. 10 p. 253 - 257

0898-6568

We examined some of the signalling events in the negative modulation of isoproterenol-induced stimulation of contractility in rat isolated atria. Isoproterenol-mediated positive inotropic response is accompanied 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 contractility. Inhibitors of calcium flux or calcium calmodulin, but not of protein kinase C, abrogated these mechanisms. The existence of a modulatory negative inotropic-cyclic GMP-mediated mechanism limiting the effect of beta-adrenergic stimulation in myocardium is discussed.