Hypertension, Vol 22, 339-347, Copyright © 1993 by American Heart Association
M Burnier, B Rutschmann, J Nussberger, J Versaggi, S Shahinfar, B Waeber and HR Brunner
This study was designed to evaluate in healthy volunteers the renal
hemodynamic and tubular effects of the orally active angiotensin II
receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was
administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a
low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study.
The two 6-day diet periods were separated by a 5-day washout period. On day
6, the subjects were water loaded, and blood pressure, renal hemodynamics,
and urinary electrolyte excretion were measured for 6 hours after a single
100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced
no significant changes in blood pressure, glomerular filtration rate, or
renal blood flow in these water-loaded subjects, whatever the sodium diet.
In subjects on a low-salt diet, losartan markedly increased urinary sodium
excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The
fractional excretion of endogenous lithium was unchanged, suggesting no
effect of losartan on the early proximal tubule in our experimental
conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to
13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/-
6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium,
calcium, and phosphate. In subjects on a high-salt diet, similar effects of
losartan were observed, but the changes induced by the angiotensin II
antagonist did not reach statistical significance. In addition, losartan
demonstrated significant uricosuric properties with both sodium
diets.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects
Hypertension Division, University Hospital, Lausanne, Switzerland.
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