CIRCULATING ANGIOTENSIN-II AND RENAL SODIUM HANDLING IN MAN - A DOSE-RESPONSE STUDY

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind pla cebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or long of angiotensin II min-1 kg-1 ove r 80 min. Subjects were studied while seated, and stood every 20 min f or urine collection. 3. Angiotensin II produced a dose-dependent antid iuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4+/-1.77, -1.26+/-0.49 (P< 0.05), -2.75+/-1.23 (P<0.05), -4.21+/-0.82 (P<0.05) a nd -6.51+/-1.07 (P<0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min -1 kg-1. The urinary sodium excretion, in mumol/min expressed as the c hange from baseline with increasing dose of angiotensin, was: 9.5+/-21 .2, -18.9+/-29.6, -37.0+/-11.6 (P<0.05), -67.7+/-19.6 (P<0.01) and -63 .8+/-14.3 (P<0.01). 5. The fractional distal reabsorption of sodium, d etermined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-r esponse curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodiu m reabsorption.