Effects of prostaglandin synthesis inhibitors on the renin-angiotensin system and renal function.
Equal doses (8 mg/kg) of the nonsteroidal antiinflammatory drugs indomethacin, naproxen, and sulindac and a large dose of sulindac (32 mg/kg) were administered intragastrically to conscious rats after a normal sodium diet, furosemide stimulation, and a low sodium diet for 8 days. Indomethacin, naproxen, and the high dose sulindac (32 mg/kg) decreased urinary prostaglandin E2 excretion significantly under all experimental conditions. Sulindac (8 mg/kg) suppressed prostaglandin E2 excretion after the normal and low sodium diets but not after furosemide stimulation. Indomethacin decreased plasma active renin levels under all three experimental conditions. In rats receiving a normal sodium diet, indomethacin did not affect free water clearance or renal function; however, after furosemide stimulation or a low sodium diet, indomethacin caused a significant reduction of free water clearance and glomerular filtration rate. Naproxen and sulindac (8 mg/kg) did not suppress active renin under any of the experimental conditions. However, naproxen and sulindac caused a significant reduction in free water clearance and glomerular filtration rate after furosemide stimulation and a low sodium diet. Indomethacin, naproxen, and the high dose sulindac suppressed renal prostaglandin E2 excretion under all experimental conditions. Renal prostaglandin E2 does not appear to be necessary for active renin secretion. Indomethacin is the most potent inhibitor of active renin and, therefore, most likely to cause hyporeninemia. Volume depletion appeared to sensitize the kidney to the adverse effects of nonsteroidal antiinflammatory drugs.
D000450:Aldosterone / Q000097:blood; D000818:Animals; D015232:Dinoprostone; D005665:Furosemide / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D007192:Indenes / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology*; D008297:Male; D009288:Naproxen / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D013467:Sulindac / Q000494:pharmacology*
D007192:Indenes; D011458:Prostaglandins E; D013467:Sulindac; D000450:Aldosterone; D009288:Naproxen; D005665:Furosemide; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin