INTERACTIVE EFFECTS OF INDOMETHACIN, ANGIOTENSIN-II AND FRUSEMIDE ON RENAL HEMODYNAMICS AND NATRIURESIS IN MAN

1 The responses of renal haemodynamic and natriuretic indices to the o ral prostaglandin synthetase inhibitor indomethacin (200 mg), to infus ed angiotensin II (1 ng min-1 kg-1) and to the combination of the two were studied in placebo-controlled fashion in eight normal male subjec ts both prior to and following administration of intravenous frusemide (20 mg). 2 As compared with placebo, angiotensin II infusion alone ca used significant reductions in absolute rate of sodium excretion, frac tional sodium excretion, urine flow rate and effective renal plasma fl ow (all P < 0.001 vs placebo) but had no effect on glomerular filtrati on rate. 3 The only change observed in these parameters with indometha cin alone was a small but significant reduction in urine flow rate (P < 0.005 vs placebo). 4 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, fracti onal sodium excretion, urine flow rate and effective renal plasma flow (all P < 0.0001 vs placebo) associated with a significant reduction i n glomerular filtration rate (P < 0.0001) not observed with angiotensi n II alone. 5 Frusemide administration at the midpoint of each study l imb resulted in each case in a prompt 15 to 20 fold increase in natriu resis. The renal haemodynamic and natriuretic effects of angiotensin I I, indomethacin and their combination were not qualitatively different from those observed in the pre-frusemide phase. 6 Our findings provid e a clear demonstration in man of the important homeostatic role of re nal prostaglandins in preserving renal function, particularly glomerul ar filtration, under conditions of elevated circulating angiotensin II .