ANTITHROMBOTIC ACTIVITY OF NICARDIPINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Calcium metabolism appears to be altered in human and experimental hyp ertension, which represents an important risk factor for thrombotic ev ents. We investigated the possible effect of the calcium antagonist ni cardipine on a model of experimental venous thrombosis in spontaneousl y hypertensive rats (SHR). Thrombus formation was highly enhanced in S HR with respect to normotensive Wistar Kyoto rats (WKY). Nicardipine, when administered orally (10 mg kg(-1)) at a single dose or once a day for three days, completely counteracted the increase in thrombus size caused by hypertension. Furthermore, a significant rise in prostacycl in production from aortic tissue [19.2+/-1.5 vs 13.2+/-2.4 ng (mg dry tissue)(-1)], associated with a fall in thromboxane A(2) release from activated platelets (328.3+/-74.6 vs 705.0+/-88.1 ng ml(-1)), was obse rved in nicardipine-treated SHR. Plasma triglyceride and free fatty ac id levels were also lowered by drug administration. Our results sugges t that the actions of nicardipine on calcium metabolism result in anti thrombotic effect through an increased availability of vasodilating ei cosanoids in vessel walls and through a reduced amount of prothromboti c agents (thromboxane, free fatty acids).