The effects of sulindac and indomethacin on the anti-hypertensive and diuretic action of hydrochlorothiazide in patients with mild to moderate essential hypertension

Abstract

In this double-blind two period crossover study, we investigated the effect of indomethacin and sulindac on blood pressure in 25 hypertensive patients being treated with hydrochlorothiazide. The study consisted of seven 4 week periods. In the first and the last period the patients took placebos, in period two, four and six they were treated with hydrochlorothiazide 50 mg once daily alone, and in the third and fifth period hydrochlorothiazide 50 mg once daily was given in combination with either indomethacin 50 mg twice daily or sulindac 200 mg twice daily in double-blind random order. Blood pressure, measured by sphygmomanometer and arteriosonde, and body weight were determined every 2 weeks. Compared with placebo hydrochlorothiazide decreased the mean arterial pressure by 8%. Addition of both indomethacin and sulindac resulted in only slight and generally similar changes of this blood pressure lowering effect. This was found both for the whole group and when both treatment sequence groups were analysed separately. In contrast to sulindac, indomethacin attenuated the hydrochlorothiazide-induced decreases of body weight, plasma potassium and the increase of plasma renin activity. Both non-steroidal anti-inflammatory drugs (NSAID) reduced the 24 h urinary excretion of prostaglandins (PGs), i.e. PGF2 alpha, 6 ketoPGF1 alpha and thromboxane B2 except PGE2. From this study it can be concluded that, in contrast to sulindac, indomethacin attenuated the diuretic action of hydrochlorothiazide, however apparently without consequences for its long-term blood pressure lowering effect. This study does not support the hypothesis that the difference between the two NSAIDs can be explained by different effects on renal PG synthesis.