Interactive effects of indomethacin, angiotensin II and frusemide on renal haemodynamics and natriuresis in man.
The responses of renal haemodynamic and natriuretic indices to the oral prostaglandin synthetase inhibitor indomethacin (200 mg), to infused angiotensin II (1 ng min-1 kg-1) and to the combination of the two were studies in placebo-controlled fashion in eight normal male subjects both prior to and following administration of intravenous frusemide (20 mg). As compared with placebo, angiotensin II infusion alone caused significant reductions in absolute rate of sodium excretion, fractional sodium excretion, urine flow rate and effective renal plasma flow (all P < 0.001 vs placebo) but had no effect on glomerular filtration rate. The only change observed in these parameters with indomethacin alone was a small but significant reduction in urine flow rate (P < 0.005 vs placebo). As compared with the effects of angiotensin II alone, indomethacin pre-treatment followed by angiotensin II infusion led to much greater falls in absolute rate of sodium excretion, fractional sodium excretion, urine flow rate and effective renal plasma flow (all P < 0.0001 vs placebo) associated with a significant reduction in glomerular filtration rate (P < 0.0001) not observed with angiotensin II alone. Frusemide administration at the midpoint of each study limb resulted in each case in a prompt 15 to 20 fold increase in natriuresis. The renal haemodynamic and natriuretic effects of angiotensin II, indomethacin and their combination were not qualitatively different from those observed in the pre-frusemide phase. Our findings provide a clear demonstration in man of the important homeostatic role of renal prostaglandins in preserving renal function, particularly glomerular filtration, under conditions of elevated circulating angiotensin II.
Department of Pharmacology and Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
J G
JG
Motwani
A D
AD
Struthers
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004347:Drug Interactions; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D016037:Single-Blind Method; D013607:Tablets
D013607:Tablets; D000804:Angiotensin II; D005665:Furosemide; D007213:Indomethacin