Mechanisms of the antinatriuretic action of physiological doses of angiotensin II in man.
1. Angiotensin II (ANG II; 1 ng min-1 kg-1) or 5% (w/v) D-glucose (placebo) was infused in six normal male volunteers, pretreated with 500 mg of lithium carbonate, who were undergoing maximal water diuresis. 2. This dose of ANG II caused a circulating increment within the physiological range (27 +/- 4 to 48 +/- 9 pmol/l). 3. Compared with placebo, ANG II caused a significant fall in urinary sodium excretion (113 +/- 13 to 82 +/- 10 mumol/min). This antinatriuretic effect occurred without a fall in creatinine clearance (107 +/- 3 versus 113 +/- 3 ml/min). 4. ANG II caused a significant fall in fractional lithium clearance (28 +/- 2 to 23 +/- 2%). This may indicate a proximal tubular effect of ANG II. 5. ANG II also reduced fractional distal delivery [(sodium clearance plus free water clearance) divided by creatinine clearance], another measure of proximal tubular outflow. A parallel change in these two separate markers of proximal function supports an action of ANG II at this nephron segment. 6. Furthermore, the antinatriuretic effect of ANG II was unlikely to be due to stimulation of aldosterone secretion because (a) the fall in sodium excretion was temporally dissociated from the rise in aldosterone secretion, (b) potassium excretion also tended to fall during ANG II infusion and (c) aldosterone has a distal nephron effect, while, in this study, proximal nephron fractional reabsorption of sodium increased and distal nephron fractional reabsorption of sodium was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Seidelin
P H
PH
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital, Scotland, U.K.
McMurray
J J
JJ
Struthers
A D
AD
D000328:Adult; D000804:Angiotensin II / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D014554:Urination
D000804:Angiotensin II; D012964:Sodium