Converting enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: Evidence for a kinin-dependent mechanism

Abstract

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-PGF_1α, 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-PGF_1α 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-PGF_1α 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.