Comparison of the vasodepressor action of ZK 36 374, a stable prostacyclin derivative, PGI 2 and PGE 1 with their effect on platelet aggregation and bleeding time in rats

Abstract

ZK 36 374, a new, chemically stable prostacyclin derivative, was compared with PGE 1 and PGI 2 with respect to its action on platelet aggregation in vitro, on bleeding time and on arterial blood pressure in conscious rats. The time of occlusion of a hole in a polyethylene (PE) tube of an AV-shunt between the left carotid artery and the right jugular vein by a microthrombus was considered as an index of bleeding time. All three substances inhibited the ADP-induced aggregation of human and rat platelets. In human PRP, ZK 36 374 was 17 times more active than PGE 1 and 2 – 5 times as potent as PGI 2. In contrast, in rat PRP, PGI 2 was 9.2 and 3.4 times as potent as PGE 1 and ZK 36 374, respectively. Similar differences in potency were found in the in vivo experiments where these substances given by an intravenous infusion to conscious rats prolonged bleeding time and depressed mean arterial pressure in a dose-dependent manner. ZK 36 374 was also orally active. At oral doses of 1, 2 and 3 mg/kg this new compound caused a dose-dependent prolongation of bleeding time and a fall in arterial blood pressure. In conclusion, the results show that ZK 36 374 is an intravenously and orally active prostacyclin derivative which may be of therapeutic value for occlusive peripheral vascular diseases.