Effect of SIN-1 in rat ventricular myocytes: Interference with β-adrenergic stimulation

We have examined the effects of the nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on Ca 2+ transients, L-type Ca 2+ current (I Ca,L), and cGMP/cAMP content in electrically-stimulated rat ventricular myocytes in the absence and presence of the β-adrenergic stimulation with isoproterenol. SIN-1 had no effect at low concentrations, but decreased the amplitude of electrically-induced Ca 2+ transients at higher concentrations. SIN-1 attenuated the increase in Ca 2+ transients induced by isoproterenol in a concentration-dependent manner. SIN-1 Also reduced the amplitude of caffeine-induced Ca 2+ transients, and the increase in I Ca,L induced by isoproterenol. These effects of SIN-1 were associated with an increased cGMP and a decreased cAMP content in ventricular myocytes in either the absence or presence of isoproterenol. These data suggest that the inhibitory effect of SIN-1 on basal and β-adrenergic stimulated Ca2+ signal in ventricular myocytes could be due to the depression in the SR function and I Ca,L, possibly mediated by a cGMP/cAMP-dependent mechanism. Taken together, the present study supports the idea that NO acts as an inhibitory modulator of the cardiac function during pathological conditions associated with an abnormal production of NO such as septic shock. © 2002 Published by Elsevier Science Inc.link_to_subscribed_fulltex