TY - JOUR T1 - Nitric Oxide Selectively Inhibits Intracellular Ca<sup>++</sup>Release Elicited by Inositol Trisphosphate but not Caffeine in Rat Vascular Smooth Muscle JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 16 LP - 21 VL - 285 IS - 1 AU - Junzhi Ji AU - Christina G. Benishin AU - Peter K. T. Pang Y1 - 1998/04/01 UR - http://jpet.aspetjournals.org/content/285/1/16.abstract N2 - The present study was designed to investigate whether nitric oxide (NO) could interfere with intracellular Ca++ release through different pathways in vascular smooth muscle. Phasic contractions of rat aorta induced by phenylephrine or caffeine in Ca++-free solution were used as an indicator of intracellular Ca++release through the inositol 1,4,5-triphosphate receptor pathway and the ryanodine receptor pathway, respectively. In addition, cytoplasmic Ca++ concentration ([Ca++]i) in vascular smooth muscle cells was determined by fluorescence measurement. Acetylcholine (ACh) inhibited the phenylephrine-evoked phasic contractions in Ca++-free solution in endothelium-intact but not -denuded aortic rings in a dose-dependent manner. However, ACh did not affect the action of caffeine. The inhibition by ACh was blocked completely by the NO synthase inhibitor Nω-nitro-l-arginine, which could be reversed totally by l-arginine but not d-arginine. Methylene blue, a soluble guanylate cyclase inhibitor, also abolished the inhibition by ACh. Sodium nitroprusside, an NO donor, attenuated the phenylephrine- but not caffeine-induced phasic contractions in denuded aortic rings in Ca++-free solution. The effect of sodium nitroprusside was reversed substantially by methylene blue. Furthermore, sodium nitroprusside inhibited the elevation of [Ca++]i induced by phenylephrine in vascular smooth muscle cells isolated from rat aorta in the absence of extracellular Ca++, which could be abolished significantly by methylene blue. These results suggest that NO selectively inhibits intracellular Ca++ release stimulated by inositol 1,4,5-triphosphate, but not caffeine in vascular smooth muscle. The American Society for Pharmacology and Experimental Therapeutics ER -