Suppression of plasma renin activity by indomethacin in man.

Abstract

SUMMARY The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PC) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterooe relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-bour sodium excretion by 49%, and urinary PC excretion, an indicator of renal PC synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PC synthetise activity. Whether indomethacin inhibits renin release by an intrarenal, PC-related mechanism or secondarily via sodium retention is discussed.THE RELEASE of renin, like other secretory events, probably is mediated by chemical or electrochemical signals. Although jS-adrenergic agonists are known stimuli for renin release, there is evidence that other important but undetermined mediators influence the secretion of renin. Our interest in the possibility that prostaglandin (PG) might participate in the release of renin arose from investigations on the possible role of PG's in the control of aldosterone secretion.1 Because some subjects who have previously experienced malignant hypertension have aldosterone hypersecretion that is not accompanied by renin excess, 2 the PG synthetase inhibitor, indomethacin, was given to a group of postmalignant hypertensive subjects to determine whether PG's participated in the control of their aldosterone secretion. Not only did aldosterone fall after administration of indomethacin, but plasma renin activity (PRA) was suppressed in parallel. To determine whether the observed suppression of PRA by indomethacin was a general phenomenon and to examine the extent to which it related to sodium retention, the effect of indomethacin on PRA was evaluated in normal volunteer subjects. In addition, we studied the effect of indomethacin on the abrupt rise in PRA that occurs within minutes after intravenous administration of furosemide.Because the increase in PRA after orally administered furosemide is used as a diagnostic stimulus in the characterization of hypertension with suppressed renin, 3 indometh- acin's possible interference w...

The effects of cilazapril alone and in combination with frusemide in healthy subjects.

“…The ability of frusemide to stimulate the renin angiotensin system was evident from 5 min and reached maximum at 10 min which is consistent with previous reports (Frolich et al, 1976;Johnston et al, 1986;Mackay et al, 1984). The increases in renal plasma flow following frusemide have been reported before (Mackay et al, 1984) and are critically dependent on salt balance.…”

“…Frusemide causes acute increases in plasma renin activity (Frolich et al, 1976;Johnston et al, 1986) and prostaglandin excretion (Mackay et al, 1984). Captopril has previously been shown to inhibit the diuretic responses to frusemide in animals, and in dogs there is evidence that captopril abolishes the acute increases in renal blood flow produced by intravenous frusemide (Johnston et al, 1984).…”

Cortical and Papillary Micropuncture Examination of Chloride Transport in Segments of the Rat Kidney during Inhibition of Prostaglandin Production

“…Our study, therefore, lends support to previous reports which have advanced evidence that nonsteroidal anti-inflammatory agents result in sodium chloride retention (3)(4)(5). The fact that two structurally different nonsteroidal anti-inflammatory drugs had similar effects on chloride transport in each of the segments examined, is evidence against nonspecific, nonprostaglandin-mediated effects.…”

“…It has been suggested that nonsteroidal antiinflammatory drugs may promote salt retention (3)(4)(5). Furthermore, these agents are generally believed to act by inhibiting endogenous prostaglandin production.…”

Contribution of prostaglandins to the systemic and renal vascular response to frusemide in normal man.

“…The inhibition by prostaglandin synthetase inhibitors of the early increase in plasma renin activity in man (Frolich et al, 1976;Tan & Mulrow, 1977;Goldiner et al, 1981) has been confirmed in this study, although such an effect was only significant 5 and 40 min after frusemide. However there was a tendency towards lower levels of PRA at all times after frusemide suggesting that at least part of the mechanism determining renin release is prostaglandin dependent.…”