Inhibition by SK&F96365 of NO‐mediated relaxation induced by Ca2+ ‐ATPase inhibitors in rat thoracic aorta

1 We investigated the effect of SK&F96365, a putative inhibitor of receptor‐operated Ca2+ entry, on the endothelium‐dependent, NO‐mediated relaxation and cyclic GMP formation induced by Ca2+‐ATPase inhibitors in rat thoracic aorta. 2 SK&F96365 inhibited cyclopiazonic acid or thapsigargin‐induced relaxation and cyclic GMP formation mediated by a constitutive NO synthase, which is known to be activated by the Ca2+ that enters into the endothelial cells via plasma membrane Ca2+ channels subsequent to depletion of stored Ca2+ by Ca2+‐ATPase inhibitors. 3 SK&F96365 also inhibited relaxation and cyclic GMP formation induced by acetylcholine, without affecting those induced by nitroprusside and A23187. 4 Ni2+ attenuated relaxation and cyclic GMP formation induced by cyclopiazonic acid and acetylcholine. 5 In contrast, the voltage‐dependent Ca2+ channel blocker, nifedipine, did not affect the relaxation caused by Ca2+‐ATPase inhibitors. 6 These results suggest that endothelium‐dependent, NO‐mediated relaxation of the arteries induced by Ca2+‐ATPase inhibitors is triggered by the Ca2+ that enters into endothelial cells via receptor‐operated channels (SK&F96365‐sensitive channels) subsequent to depletion of stored Ca2+ as a result of inhibition of the Ca2+‐ATPase (Ca2+ pump) of the stores.