Sulindac and ibuprofen inhibit furosemide-stimulated renin release but not natriuresis in men on a normal sodium diet.
We compared the effect of two commonly prescribed nonsteroidal anti-inflammatory drugs, ibuprofen and sulindac, and placebo on intravenous furosemide-induced natriuresis and renin stimulation in 11 healthy male volunteers, consuming a 100 mEq sodium, 80 mEq potassium diet. Chronic (6-day) therapy with each agent was followed by a 1-week washout period. There were no significant treatment-related differences in either urine volume or sodium excretion for any of the designated collection periods or for the cumulative value for the 4 h after furosemide administration. Similarly, differences among groups were not observed for creatinine clearance, urinary potassium and urinary chloride excretion. Mean basal plasma renin activity levels prior to furosemide administration on day 6 were significantly lower in the presence of ibuprofen (1.5 +/- 2.0 ng/ml/h;p less than 0.01) and sulindac (2,3 +/- 0.9 ng/ml/h; p less than 0.05), compared with placebo (3.3 +/- 1.1 ng/ml/h); the difference between the two NSAIDs was also significant (p less than 0.05). Mean plasma renin activity levels in the 4 h after furosemide increased significantly at all time points in comparison to basal values, but were significantly less for ibuprofen and sulindac groups in the first hour. Our data suggest that the natriuresis following intravenous furosemide in men consuming a normal sodium intake is not prostaglandin-dependent. Furthermore, the observation that sulindac suppressed basal and stimulated plasma renin activity levels, albeit to a lesser extent than ibuprofen, questions the claim that sulindac "spares' the kidney and compels further evaluation of this issue.
D000328:Adult; D002712:Chlorides / Q000652:urine; D004032:Diet; D004311:Double-Blind Method; D005665:Furosemide / Q000037:antagonists & inhibitors*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000008:administration & dosage; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000008:administration & dosage*; D013467:Sulindac / Q000494:pharmacology*; D013997:Time Factors
D002712:Chlorides; D007192:Indenes; D013467:Sulindac; D005665:Furosemide; D012964:Sodium; D012083:Renin; D011188:Potassium; D007052:Ibuprofen