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.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D002118:Calcium