Vol. 285, Issue 1, 16-21, April 1998

Nitric Oxide Selectively Inhibits Intracellular Ca⁺⁺ Release Elicited by Inositol Trisphosphate but not Caffeine in Rat Vascular Smooth Muscle

Junzhi Ji, Christina G. Benishin and Peter K. T. Pang

Department of Physiology, University of Alberta, Edmonton, Alberta, Canada

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 N-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.