Effects of isoflurane on receptor-operated Ca2+ channels in rat aortic smooth muscle

We have investigated the effects of isoflurane on receptor-operated Ca2+ channels (ROC) in vascular smooth muscle. In isolated rat thoracic aortic rings denuded of endothelium, the effects of isoflurane on phenylephrine-induced contraction and Ca2+ influx were evaluated in the presence of supramaximal doses of nifedipine or verapamil. Under isometric tension recording, the aortic rings were precontracted by phenylephrine 300 nmol litre(-1) and exposed to 1.2%, 2.3% or 3.5% isoflurane. Phenylephrine-induced precontraction was enhanced with 2.3% isoflurane by mean 8.1 (SD 9.3) % (P<0.05 vs 0% isoflurane). The constrictor effect of 2.3% isoflurane was not inhibited by depletion of intracellular Ca2+ stores with ryanodine 20 mu mol litre(-1), but was abolished in a Ca2+-free solution or by SK&F 96365 30 mu mol litre(-1), an ROC blocker. Isoflurane-induced contraction was accompanied by increased intracellular free Ca2+ concentration, monitored using fura PE3. Unidirectional Ca-45(2+) influx measurement in phenylephrine-stimulated aortic strips revealed that the mean amount of Ca2+ influx was significantly (P<0.05) enhanced by 1.2% and 2.3% isoflurane, which were 117.1% and 119.7% of control values, respectively. Our results strongly suggest that isoflurane enhanced Ca2+ influx through ROC that had been submaximally activated by phenylephrine.