Indomethacin reduces the antihypertensive action of enalapril

We evaluated the influence of indomethacin on the pharmacological actions of Enalapril in 9 uncomplicated essential hypertensives. While on chronic treatment with Enalapril, these patients randomly received indomethacin (50 mg bid) or a corresponding placebo for 1 week and the opposite treatment after a 2 week interval. Indomethacin, which decreased serum thromboxane B2 and urinary 6-keto prostaglandin-F1 alpha, reduced the plasma renin activity (PRA) increased by Enalapril. Indomethacin did not modify serum ACE, whose activity had been reduced by the ACE inhibitor. Mean blood pressure (MBP) values, which were significantly and to a similar extent reduced by Enalapril at the beginning of the cross-over, after placebo addition and at the end of the two week interval, were significantly increased by indomethacin, despite being still significantly lower than baseline values. These data show that systemic and renal prostaglandin (PG) synthesis inhibition induced by indomethacin can blunt the antihypertensive effect of chronic Enalapril treatment in patients with essential hypertension.