Antithrombotic activity of nicardipine in spontaneously hypertensive rats.
Calcium metabolism appears to be altered in human and experimental hypertension, which represents an important risk factor for thrombotic events. We investigated the possible effect of the calcium antagonist nicardipine on a model of experimental venous thrombosis in spontaneously hypertensive rats (SHR). Thrombus formation was highly enhanced in SHR 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 prostacyclin production from aortic tissue [19.2 +/- 1.5 vs 13.2 +/- 2.4 ng (mg dry tissue)-1], associated with a fall in thromboxane A2 release from activated platelets (328.3 +/- 74.6 vs 705.0 +/- 88.1 ng ml-1), was observed in nicardipine-treated SHR. Plasma triglyceride and free fatty acid levels were also lowered by drug administration. Our results suggest that the actions of nicardipine on calcium metabolism result in antithrombotic effect through an increased availability of vasodilating eicosanoids in vessel walls and through a reduced amount of prothrombotic agents (thromboxane, free fatty acids).
Cignarella
A
A
Institute of Pharmacological Sciences, University of Milan, Italy.
Bertozzi
D
D
Zaarour
C
C
Puglisi
L
L
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000032:analysis; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013924:Thrombophlebitis / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D005343:Fibrinolytic Agents; D014280:Triglycerides; D002784:Cholesterol; D009529:Nicardipine