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...

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Digoxin serum and urine levels were determined by radioimmunoassay in 6 subjects (4 patients with heart disease and 2 volunteers without heart disease) who had been maintained on oral digoxin (0.25 or 0.5 mg daily). Observations were made during a 3-day control period and then during 8 days of concomitant digoxin and oral furosemide (40 mg daily) therapy. Serum digoxin levels determined 10 and 24 hr after each dose of digoxin averaged 1.2+/-0.1 ng/ml (M+/-SE) during control and 1.3+/-0.1 during the last 3 days on digoxin and furosemide. The daily urinary excretion of digoxine averaged 51+/-6% of the oral dose during control and 52+/-6 during the entire period of furosemide administration. The renal clearance of digoxin and creatinine averaged 94+/-7 and 87+/-11 ml/min, respectively, during control; corresponding values were 88+/-8 and 85+/-9 for urine collections demonstrating a distinct diuretic effect of furosemide and 87+/-8 and 75+/-10 for urine collections not demonstrating such an effect during diuretic therapy. The results suggest that the diuretic effect of furosemide does not significantly affect the excretion of digoxin