Anti-thrombotic activity of PDR, a newly synthesized l-Arg derivative, on three thrombosis models in rats

Abstract

The possibility of a newly synthesized l-arginine derivative, polyaspartoyl- l-arginine (PDR), as a novel anti-thrombotic agent and its mode of action were investigated. The anti-platelet effects of PDR in rats ex vivo, anti-thrombotic effects in three thrombosis models in rats and its effect on some autacoids (nitric oxide [NO], thromboxane [TXA 2] and prostacyclin [PGI 2]) were studied. PDR (i.g.) significantly inhibited ADP-, collagen- or thrombin-induced rat platelet aggregation. In arteriovenous shunt model and ferric chloride-induced arterial thrombosis model in rats, PDR (i.g.) significantly reduced the thrombus weight. In electrical stimulation-induced arterial thrombosis in rats, PDR (i.v.) dose-dependently prolonged the thrombus occlusion time (OT). PDR increased the concentration of NO in plasma. In contrast with aspirin (ASA), PDR did not influence on the TXA 2 and PGI 2 levels in plasma. In conclusion, PDR is provided with significant inhibitory effect on platelet aggregation and prevention effect on platelet related thrombosis, which is probably attributed to its inhibition on platelet function by l-arginine–NO pathway. The results demonstrate that PDR is a novel, oral and venous effective platelet aggregation inhibitor and has a possibility used as an anti-thrombotic agent.