Effect of Ca++ Antagonists on the Metabolism of Prostaglandin in the Vessel Walls

Prostacyclin (PGI2), a platelet aggregation inhibitor produced and released from the endothelial cells of the vascular vessels, is though to be concerned with the development of thrombosis and atherosclerosis. In the present experiment using rat aorta, we studied the influence of Ca++ antagonists of the release of PGI2.The PGI2 activity was measured by the inhibitory effect of ADP-induced human platelet aggregation. Ca++ antagonists used are Diltilzem, Verapamil and Cinnarizine. The influence of Ca++ ionophore A23187 and dibutylyl c-AMP was also studied.As a result, Ca++ antagonists were all shown to have an activity to increase the PGI2 release from the vascular walls. When the aorta was treated with A23187 having an activity to raise Ca++ concentrations in cells, the PGI2 release was accelerated. However, the c-AMP treatment had no significant influence on the PGI2 release.From these findings it was surmised that the PGI2 release-increasing activity of Ca++ antagonists would not be via changes in the concentrations of Ca++ or c-AMP. Then, phospholipase A2 was inhibited with hydrocortisone and at the same time the aorta was incubated in a buffer supplemented exogenously with arachidonic acid, to which were added Ca++ antagonists to study the influence of Ca++ antagonists on the arachidonic acid metabolic pathway following the stage of phospholipase A2.As a result, Ca++ antagonists increased the amount of PGI2 produced and released from exogenous arachidonic acid. However, A23187 and c-AMP had no influence on this route.As can be seen from the results above, Ca++ antagonists—Diltiazem, Verapamil and Cinnarizinezine—increase the PGI2 release from the vascular wall but this effect is observed in the arachidonic acid metabolis pathway following the stage of phospholipase A2. Therefore it was suggested that the mode of action of these Ca++ antagonists would be independent on changes in the concentration of Ca++ and c-AMP.