NITRIC-OXIDE SELECTIVELY INHIBITS INTRACELLULAR CA-MUSCLE(+ RELEASE ELICITED BY INOSITOL TRISPHOSPHATE BUT NOT CAFFEINE IN RAT VASCULAR SMOOTH)

The present study was designed to investigate whether nitric oxide (NO ) could interfere with intracellular Ca++ release through different pa thways in vascular smooth muscle. Phasic contractions of rat aorta ind uced by phenylephrine or caffeine in Ca++-free solution were used as a n indicator of intracellular Ca++ release through the inositol 1,4,5-t riphosphate receptor pathway and the ryanodine receptor pathway, respe ctively. In addition, cytoplasmic Ca++ concentration ([Ca++](i)) in va scular smooth muscle cells was determined by fluorescence measurement. Acetylcholine (ACh) inhibited the phenylephrine-evoked phasic contrac tions in Ca++-free solution in endothelium-intact but not -denuded aor tic rings in a dose-dependent manner. However, ACh did not affect the action of caffeine. The inhibition by ACh was blocked completely by th e NO synthase inhibitor N-omega-nitro-L-arginine, which could be rever sed totally by L-arginine but not D-arginine. Methylene blue, a solubl e guanylate cyclase inhibitor, also abolished the inhibition by ACh. S odium 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 substan tially 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++ releas e stimulated by inositol 1,4,5-triphosphate, but not caffeine in vascu lar smooth muscle.