Endothelium-derived relaxing factor alters calcium fluxes in rabbit aorta: a cyclic guanosine monophosphate-mediated effect.

1. Measurement of tension and 45Ca influx and efflux were used to study the effects of endothelium-derived relaxing factor (EDRF), sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) on contractile responses and calcium movements in aortic ring preparations of the rabbit. 2. EDRF activity, induced by stimulating endothelium-containing rings with acetylcholine, was associated with relaxation of noradrenaline-constricted rings and with a marked reduction of noradrenaline-stimulated increase in calcium influx. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations. 3. EDRF also inhibited noradrenaline-stimulated calcium efflux. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations, both in the presence and absence of extracellular calcium. 4. The vascular smooth muscle relaxant effect of EDRF and of nitrovasodilators may be effected by a cyclic GMP-mediated reduction of cytosolic calcium, through both inhibition of calcium influx and reduction of intracellular calcium release.