ROLE OF INTRACELLULAR CA2+ IN EDRF RELEASE IN RAT AORTA

In rings of rat aorta, cyclopiazonic acid (CPA), a selective inhibitor of the internal membrane Ca2+-pump ATPase, gradually initiated a conc entration-dependent contraction which was much less in endothelium-int act than in endothelium-denuded rings. In phenylephrine-precontracted rings with intact endothelium, CPA, like acetylcholine, produced endot helium-dependent relaxations in a concentration-dependent manner. Thes e were nearly abolished by methylene blue (MB) or N-G-nitro-L-arginine methylester (L-NAME). This inhibitory effect of L-NAME was reversed b y L-arginine but not by D-arginine, indicating that CPA induced a rele ase of endothelium-derived relaxing factor (EDRF) from endothelial cel ls leading to smooth muscle relaxation. Concentration-dependent relaxa tions induced by sodium nitroprusside, which is thought to act by rele asing nitric oxide, were not inhibited by L-NAME, but were inhibited s imilarly by MB in endothelium-intact and -denuded rings. These results indicate that CPA causes EDRF-release from endothelial cells and supp ort the recent hypothesis that release of intracellular Ca from stores is the initiating factor in EDRF release, possibly allowing ongoing C a entry to sustain release.