Mechanism of furosemide-induced natriuresis by direct stimulation of renal prostaglandin E2.
Studies were conducted to investigate the interaction of renal prostaglandin E2 (PGE2) production and the renin-angiotensin system in the mechanism of furosemide-induced natriuresis. In conscious rabbits with permanent urinary bladder cannulation, furosemide in vivo (10 mg/kg) increased urinary water, sodium, and PGE2 excretion and plasma renin activity (PRA) over 50 min. Furosemide administered in vivo enhanced renal papillary but not cortical in vitro PGE2 biosynthesis. Prior administration of indomethacin at 2 mg/kg augmented the saluretic effect of furosemide, decreased its effect on UPGE2 V, abolished the rise in PRA, and reduced cortical but not papillary PGE2 biosynthesis. However, at 10 mg/kg, indomethacin reduced the saluretic effect of furosemide and eliminated the increase in UPGE2 V with continued suppression of PRA. Direct addition of furosemide in vitro to the incubation medium (10(-5) and 10(-3) M) markedly augmented papillary PGE2 synthesis. It is concluded that furosemide stimulates renal papillary PGE2 biosynthesis directly without mediation by angiotensin II, resulting in an increase in UPGE2 V, and the enhanced or inhibitory effect of indomethacin on furosemide-induced natriuresis is dose related and dependent on the degree of PGE2 synthesis inhibition in the presence of suppressed PRA, which occurred at all doses studied.
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone; D005665:Furosemide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011458:Prostaglandins E / Q000502:physiology* / Q000652:urine; D011817:Rabbits; D012964:Sodium / Q000652:urine
D011458:Prostaglandins E; D000804:Angiotensin II; C009210:sarleucin; D005665:Furosemide; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin