Hypertension, Vol 21, 704-713, Copyright © 1993 by American Heart Association
MR Goldberg, W Tanaka, A Barchowsky, TE Bradstreet, J McCrea, MW Lo, EJ McWilliams Jr and TD Bjornsson
Losartan is an orally active, nonpeptide angiotensin II (Ang II) (site- 1)
receptor antagonist. We conducted a multiple-dose study in healthy male
volunteers to investigate the tolerability, blood pressure effects, and
changes in plasma renin activity (PRA) and plasma Ang II concentration
associated with once-daily administration of 100 mg losartan for a week.
Subjects were studied on a standardized sodium diet (24-hour urinary sodium
excretion, 98 +/- 37 [SD] mEq per 24 hours on the placebo run-in day).
Measurements of blood pressure, heart rate, PRA, Ang II, and aldosterone
were taken during a placebo run-in day and after single and multiple (7
days) daily doses of losartan (100 mg, n = 10) or placebo (n = 4). Ang II
was measured specifically by high performance liquid chromatography coupled
with radioimmunoassay. In subjects given losartan, respective decreases
(systolic/diastolic) from run-in in supine blood pressure 6 hours after
dosing were (mean +/- SD), compared with the placebo run-in day, first
dose: -8.8 +/- 9.6/- 6.8 +/- 5.0, last dose: -11.6 +/- 8.9/-7.0 +/- 4.8 mm
Hg (p < 0.05 for all changes). At this 6-hour time point, corresponding
increases from run-in in PRA were from 1.2 +/- 0.6 to 12.0 +/- 6.3 (first
dose) and 9.6 +/- 4.9 (last dose) ng angiotensin I per milliliter per hour
and in Ang II were from 4.3 +/- 1.7 to 72.4 +/- 33.3 and 45.7 +/- 14.1
pg/mL. All changes in PRA and Ang II were statistically significant within
the losartan-treated group, and the biochemical changes were significantly
greater than those in the placebo-treated group. The increment in Ang II
was less after the last dose than after the first (p < 0.05). The drug
was well tolerated by all subjects. These data indicate that, under the
conditions of this study, losartan administration (100 mg/day for eight
doses over 9 days) results in treatment-related decreases in blood pressure
and increases in PRA and Ang II octapeptide.
ARTICLES
Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers
Merck Research Laboratories, West Point, PA 19486.
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