ACTIONS OF 3-MORPHOLINOSYDNONIMIN (SIN-1) ON RABBIT ISOLATED PENILE ERECTILE TISSUE

The effects of the NO-donor 3-morpholinosydnonimin (SIN-1) on isometri c tension, cyclic guanosine 3',5'-monophosphate (cyclic GMP) accumulat ion and neuronal release of H-3-noradrenaline were investigated in rab bit isolated corpus cavernosum (CC), and compared to the actions of so dium nitroprusside (SNP) and the cyclic GMP-specific phosphodiesterase inhibitor zaprinast. SIN-1, zaprinast and SNP concentration dependent ly relaxed rabbit CC preparations contracted by 1 muM. phenylephrine. All the drugs were highly effective, and the order of potency was SNP > zaprinast > SIN-1. SIN-1 had a biphasic effect on contractions evoke d by electrical field stimulation of nerves: at low concentrations (1 and 10 muM.), SIN-1 inhibited the contractions, while at concentration s greater-than-or-equal-to 100 muM., the contractions were again incre ased. There were no changes in baseline tension. Electrically evoked c ontractions were inhibited by zaprinast in a concentration-dependent m anner. Compared with controls, 1 mM. SIN-1 caused a significant (p < 0 .05) increase in both the basal efflux and in the electrically induced release of H-3 from CC preparations incubated with H-3-noradrenaline. SIN-1, zaprinast and SNP increased tissue levels of cyclic GMP. There was no positive correlation between cyclic GMP accumulation and the r elaxant effects of the drugs. The effects of SIN-1 and SNP on the tiss ue content of cyclic GMP were not significantly affected by methylene blue, an inhibitor of soluble guanylate cyclase. It may be concluded t hat SIN-1, zaprinast and SNP are effective in relaxing isolated penile erectile tissue, and this effect is associated with an increase in th e tissue content of cyclic GMP via pathways not sensitive to methylene blue. However, additional mechanisms beside stimulation of adrenergic neurotransmission and activation of guanylate cyclase in the smooth m uscle cell seem to participate in the action of SIN-1 on rabbit penile erectile tissue.