Factors modifying the early nondiuretic vascular effects of furosemide in man. The possible role of renal prostaglandins.
Animal experiments have suggested that salt-balance, prostaglandin synthesis, and renal function are important determinants of the nondiuretic vascular effects of furosemide. To investigate the influence of these factors in humans, we studied 10 normal volunteers and five anephric patients. The volunteers were studied on three occasions: when on a 10 mEq/day sodium diet, on a 250 mEq/day sodium diet, and on a 10 mEq/day sodium diet with indomethacin, 200 mg/day. The anephric patients were studied immediately after dialysis. Plethysmographic methods were used to measure venous capacitance and blood flow in the calf before, and at 5, 10, and 15 minutes after furosemide, 80 mg, iv. Blood was obtained before and 15 minutes after furosemide for determination of plasma renin activity by radioimmunoassay and of plasma 6-keto-prostaglandin F1 alpha by chromatography-mass spectrometry. We found that furosemide significantly increased venous capacitance in the calf of the normal volunteers on a low salt diet. Indomethacin, high salt intake, or lack of renal function was sufficient to inhibit this effect. Plasma renin activity increased only in the group that had the increase in venous capacitance. Limb blood flow decreased gradually in the 15 minutes following administration of furosemide in the normal volunteers, regardless of salt balance or indomethacin, but remained unchanged in the anephric patients. Plasma 6-keto-prostaglandin F1 alpha was less than 30 pg/ml in all samples. Indomethacin concentration averaged 1.3 micrograms/ml in volunteers on the drug. To determine whether indomethacin, salt intake or renal function affected another venodilator, we studied an additional group of normal and uremic volunteers who received 0.6 mg nitroglycerin sublingually.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D004039:Diet, Sodium-Restricted; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000502:physiology*; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010991:Plethysmography; D011453:Prostaglandins / Q000097:blood / Q000502:physiology*; D011460:Prostaglandins F / Q000097:blood / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014680:Veins / Q000187:drug effects*; D014882:Water-Electrolyte Balance
D011453:Prostaglandins; D011460:Prostaglandins F; D005665:Furosemide; D012083:Renin; D005996:Nitroglycerin; D007213:Indomethacin