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.

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The present study investigates whether the synthesis of prostacyclin (PGI2) in isolated rat aorta is dependent on the state of sodium balance of the animals. Three groups of ten rats each were included into the study. Two of them were fed a diet low in NaCl for 10 days with group I receiving 0.9% saline and group II distilled water as drinking fluid. Group III received a regular rat chow containing approximately 0.8 mmol day-1 of sodium, also for 10 days. At the end of the dietary protocol, systolic arterial blood pressure was significantly higher in group I (109.9 +/- 2.4 mmHg) as compared to group II (101.0 +/- 2.4 mm Hg; P less than 0.05) and group III animals (102.2 +/- 1.6 mm Hg; P less than 0.05). Generation of PGI2-like activity was determined in portions of the animals' isolated aorta using a platelet aggregation bioassay following incubation in 0.05 M Tris buffer (pH 9.3) for 12, 15, and 30 min, respectively. During these incubation times, generation of PGI2-like activity averaged 48.6 +/- 3.5, 57.8 +/- 4.3 and 68.3 +/- 3.2 pmol mg-1 in group III animals, which had received the regular rat chow, with similar values in the low salt group II (50.2 +/- 2.5, 57.7 +/- 2.7 and 72.9 +/- 3.7 pmol mg-1). Aortic generation of PGI2-like material was significantly suppressed in the high salt group I (37.5 +/- 2.8, 46.2 +/- 3.2 and 61.3 +/- 4.0 pmol mg-1; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)