EFFECTS OF CYCLOPIAZONIC ACID AND THAPSIGARGIN ON ELECTROMECHANICAL ACTIVITIES AND INTRACELLULAR CA2-MUSCLE OF CAROTID-ARTERY OF HYPERTENSIVE RATS( IN SMOOTH)

1 The effects of cyclopiazonic acid (CPA) and thapsigargin (TG), both of which are known to inhibit sarcoplasmic reticular Ca2+-ATPase, on t he mechanical activities, intracellular Ca2+ level and electrical acti vities of smooth muscle of the carotid artery of stroke-prone spontane ously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were compa red. 2 Both CPA and TG induced elevation of tension of the smooth musc le, which was composed of a phasic and a tonic component. The level of tension attained, especially the tonic component, was greater in the preparation from SHRSP. 3 The elevation of tension was associated with an increased intracellular Ca2+ level. Both the elevation of tension and the increase in intracellular Ca2+ were diminished by the removal of extracellular Ca2+ or by the application of verapamil. 4 The restin g membrane potential of the preparations from SHRSP were depolarized t o a greater extent than those from WKY. CPA depolarized the smooth mus cle from both SHRSP and WKY, and the final level was also more depolar ized in the preparation from SHRSP. 5 These results indicate that the elevation of tension induced by these drugs is mainly due to increased Ca2+ influx through voltage-dependent Ca2+ channels, and the differen ce in the action between the preparation from SHRSP and that from WKY can be explained mainly by the changes in the channels. 6 Thus, differ ences in the action of these drugs on the tension of smooth muscle bet ween preparations from WKY and SHRSP can mainly be explained by the di fference in the membrane potential which is related to the difference in voltage-dependent Ca2+ influx.