Converting enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: evidence for a kinin-dependent mechanism.
The present study was performed to investigate the effect of the angiotensin I-converting enzyme inhibitor ramipril on vascular synthesis of prostacyclin (PGI2). Administration of ramipril (Hoe 498) to rats significantly stimulated prostacyclin (PGI2) synthesis, quantified by radioimmunoassay of its stable hydrolysis product 6-keto-PGF1 alpha, by portions of the animals' isolated aorta. This effect was maximal at a dose range of 10(-7) mol/kg ramipril. The addition of the active ramipril metabolite ramipril diacid directly into the incubation buffer at final concentrations of 10(-9), 10(-6), and 10(-4) M resulted in a dose-dependent stimulation of 6-keto-PGF1 alpha released by isolated aortic tissue. Pretreatment of rats with aprotinin (40,000 U s.c. 60 min before the incubations) attenuated the ramipril-induced effect on aortic 6-keto-PGF1 alpha synthesis. Our results show that the angiotensin I-converting enzyme inhibitor ramipril stimulates PGI2 synthesis in vascular tissue and that this effect may be secondary to changes in the activity of the kinin system.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D007705:Kinins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007705:Kinins; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D017257:Ramipril