Nitric oxide selectively inhibits intracellular Ca++ release elicited by inositol trisphosphate but not caffeine in rat vascular smooth muscle.
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 Nomega-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.
Ji
J
J
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Benishin
C G
CG
Pang
P K
PK
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D010656:Phenylephrine; D009569:Nitric Oxide; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium