title: Ebelactone B, an inhibitor of extracellular cathepsin A-type enzyme, suppresses platelet aggregation ex vivo in renovascular hypertensive rats.
abstract: The present study was undertaken to investigate whether ebelactone B, an inhibitor of bradykinin and angiotensin I hydrolysis by serine carboxypeptidase Y-like enzymes, could influence platelet aggregation ex vivo in renovascular hypertensive rats (2-kidney, 1-clip Goldblatt model, 2K1C). We found that ebelactone B (5 mg/kg) administrated subcutaneously once a day for 5 days, 5 weeks after the development of hypertension, or a single dose of ebelactone B (0.5 mg/kg) injected intravenously into 2K1C hypertensive rats before the induction of arterial thrombosis, both markedly suppressed collagen-induced platelet aggregation in whole blood. In contrast, inhibition of collagen-induced platelet aggregation was not evident in vitro after pretreatment of the blood with ebelactone B, indicating that ex vivo the antiaggregatory action of this compound can proceed through an indirect mechanism. The injection of ebelactone B did not affect the mean blood pressure of 2K1C hypertensive rats but lowered an elevated extracellular serine carboxypeptidase cathepsin A-like activity. Thus, the data indicate that ebelactone B may be a promising antiaggregatory agent in renovascular hypertension and suggest that 1 of the possible mechanisms through which it exerts this effect may be related to the suppression of cathepsin A-like activity released locally during the development of renovascular hypertension.
authors.affiliation: Department of Biology, Medical University of Bialystok, Bialystok, Poland. halost@amb.edu.pl
authors.forename: Halina
authors.initials: H
authors.lastname: Ostrowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Kalinowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Chabielska
authors.forename: Adrian
authors.initials: A
authors.lastname: Stankiewicz
authors.forename: Kamil
authors.initials: K
authors.lastname: Kruszewski
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Buczko
mesh_terms: D000818:Animals; D043402:Cathepsin A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects* / Q000201:enzymology*; D006978:Hypertension, Renovascular / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; C030795:ebelactone B; D043402:Cathepsin A