Isradipine decreases arterial thrombogenicity in rabbits

Abstract

Aim: To examine the effect of isradipine, a member of the dihydrophyridine family of calcium antagonists, on aortic and iliac wall thrombogenicity Materials and Methods: After one week of dosing, the abdominal aorta and iliac artery endothelium was abraded using fogarthy catheter. Aortic and iliac thrombogenicity was assessed, after perfusion in situ, by morphological quantification of platelet deposition using the Baumgartner technique as well as by counting the radioactivity after radiolabeling of autologous platelets with 111 in-oxine. One group of animals (n=8) were dosed for one week with isradipine 0.3 mg/kg. A second group of animals received 50mg acetylsalicylic acid (A.S.A) daily in addition, while a third group received the vehicle only. Finally a fourth group of animals (n=8) were treated with aspirin only. Results: The percentage of the denuded surface covered with contact (unspread) platelets decreased significantly (*p<0.01). From 14.7 ± 2.0 to 9.3 ± 2.1* (6.2 ± 0.8 to 3.7 ± 0.4). The amount of contact and spread of platelets was diminished from 84.9 ± 5.6 to 71.4 ± 4.4* (91.8 ± 5.3 to 75.2 ± 4.6*). Platelet thrombi decreased from 7.4 ± 0.9 to 4.6 ± 1.4* (9.4 ± 1.9 to 5.2 ± 0.7*) in the aorta and iliac artery, respectively. 111 in-oxine Platelet deposition decreased by 39.9 and 41.9%. Concomitant A.S.A-therapy not only abolished the effect of isradipine, but also ehanced thrombogenicity probably as a result of almost complete blockade of vascular PG12-production. A.S.A. alone induced an even more thrombogenic action. Conclusion: The result from both methods show that isradipine exerts significant benefits on vascular thrombogenicity most likely via enhanced PG12 formation leading to improved platelet vessel-wall interaction. This benefit can be absolished and thrombogenicity even increased by cyclo-oxygenase blockade.

Keywords

• isradipine
• arterial thrombogenicity
• rabbits