787-5 Systemic Effect of Ramipril on Endothelin, but not on Elcosanoid Levels in Patients with Coronary Artery Disease

Study aim Neurohumoral effects of ramipril (R) alone or in combination with isosorbide dinitrate (ISDN) compared to ISDN or placebo. Study design Placebo-controlled double-blind parallel group trial. Methods 32 patients with coronary artery disease (CAD) received placebo, R5 mg, ISDN 20 mg slow release b.i.d. or R + ISDN for one week. A 24 hour kinetic profile of ramipril and its metabolite, of ace activity (ACE-A) and of related hormones (renin and aldosterone), of endothelin and of prostaglandins (PG), thromboxane B2 (TXB2), PGF2a, 6-keto PGF1a, the stable metabolite of prostacyclin (PGI2-M) was studied after the first dose. Measurements were repeated after 8 days of treatment before and 3 hours after the morning dose. Results Hormone measurements are presented as means of percent difference of patients treated with R (n = 16) vs. those without ace-inhibitor (n = 16). Time (hrs) 0 1 2 3 4 6 8 24 0–8 3–8 Ramipril (mg/l) 0 8 5 4 3 2 1 0.4 1 7 Ramiprilat (mg/l) 0 6 11 10 8 7 5 1 2 14 ACE-A (%) -6 -78 -95 -98 -98 -97 -96 -80 -82 -98 Aldosteron (%) 9 -5 -31 -34 -21 -27 -23 -34 - - Renin (%) -9 -7 7 19 13 17 53 32 - - Endothelin (%) -17 -13 -25 -19 -16 -15 -4 0 - - TXB2 (%) 4 10 4 5 - 5 0 12 -3 PGF2a (%) 10 17 0 0 - 8 - 2 2 -9 PGI2-M (%) 7 0 -3 8 - -5 9 -1 -7 13 - = not done; significant differences are printed in italics (two-tailed t-test) A single oral dose of 5 mg R reduced ACE activity (p l 0.001), decreased aldosterone and increased renin (p l 0.1). R did not influence plasma levels of the vasoconstricting (TXB2, PGF2a) or vasodilating (PGI2-M) eicosanoid mediators, but decreased endothelin (p l 0.1). Conclusion R, in a dose that results in significant systemic inhibition of the renin angiotensin aldosteron system, does not induce measurable changes of circulating eicosanoid concentrations, but seems to diminish systemic release of endothelin.