Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects.
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)
Burnier
M
M
Hypertension Division, University Hospital, Lausanne, Switzerland.
Rutschmann
B
B
Nussberger
J
J
Versaggi
J
J
Shahinfar
S
S
Waeber
B
B
Brunner
H R
HR
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004573:Electrolytes / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008094:Lithium / Q000652:urine; D019808:Losartan; D008297:Male; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage; D013777:Tetrazoles / Q000494:pharmacology*; D014527:Uric Acid / Q000652:urine; D014556:Urine
D001713:Biphenyl Compounds; D004573:Electrolytes; D007093:Imidazoles; D012982:Sodium, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D014527:Uric Acid; D000450:Aldosterone; D008094:Lithium; D012083:Renin; D019808:Losartan