title: Cardiovascular actions in vitro and cardioprotective effects in vivo of nileprost, a mixed type PGI2/PGE2 agonist.
abstract: Cardiovascular, platelet- and neutrophil-inhibitory effects of the chemically stable prostacyclin analog nileprost (5-cyano-16-methyl-PGI2) (NIL, ZK 34798) were studied in vitro and in a feline model of acute myocardial ischemia in vivo. Isolated bovine coronary arteries were relaxed by NIL at low concentrations (less than 3 microM), whereas higher concentrations produced a marked vasoconstriction. NIL inhibited human platelet aggregation and reduced the coronary vascular resistance of Langendorff-perfused rabbit hearts. Myocardial contractile force and oxygen consumption were not affected. The superoxide anion generation of stimulated granulocytes was modestly antagonized by NIL. NIL (0.5 microgram/kg/min intravenously, i.v.) protected the left ventricular myocardium of cats subjected to 5 h of coronary artery ligation from ischemic injury, as evidenced by the reduction in ischemia-induced ST-segment elevation, prevention of the large increase in plasma creatinine kinase (CK), and loss of myocardial CK and free amino nitrogen. These effects and the extent of cardiac protection by NIL were comparable to those of PGI2 (0.2 microgram/kg/min), whereas PGE2 (1.5 microgram/kg/min) was less effective. The data demonstrate a combination of PGI2-like and PGE2-like activities for NIL in vitro and a significant cardioprotective action of NIL in vivo.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D015232:Dinoprostone; D004562:Electrocardiography; D011464:Epoprostenol / Q000494:pharmacology* / Q000502:physiology* / Q000627:therapeutic use / Q000031:analogs & derivatives; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000502:physiology*; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism
chemical_list: D011458:Prostaglandins E; D013481:Superoxides; D011464:Epoprostenol; D003402:Creatine Kinase; D015232:Dinoprostone; C038832:nileprost