Circulation, Vol 88, 1602-1609, Copyright © 1993 by American Heart Association
SS Gottlieb, K Dickstein, E Fleck, J Kostis, TB Levine, T LeJemtel and M DeKock
BACKGROUND. Losartan is a new specific angiotensin II receptor antagonist
with no agonist properties that provides the opportunity to study the
consequences of angiotensin II blockade. The objective of the present study
was to evaluate the hemodynamic and neurohormonal response to losartan in
patients with congestive heart failure. METHODS AND RESULTS. After baseline
hemodynamic measurements using balloon- tipped pulmonary artery and radial
arterial catheters, patients were randomized to receive a single dose of
placebo or 5, 10, 25, 75, or 150 mg losartan in a double-blind, sequential
fashion. Hemodynamic and neurohormonal parameters were then measured
periodically for 24 hours. Losartan caused vasodilation in a dose-dependent
manner. By the area- under-the-curve method, the reduction in the mean
arterial pressure and systemic vascular resistance grew larger up to a dose
of 25 mg, but the higher 75- and 150-mg doses did not produce additional
vasodilation. In response to losartan, there were compensatory increases in
both angiotensin II concentrations and in plasma renin activity, which were
greatest at the highest doses. Aldosterone concentrations were
significantly lowered with losartan. CONCLUSIONS. Blockade of the
angiotensin II receptor with the antagonist losartan causes vasodilator and
neurohormonal effects in patients with congestive heart failure. The lack
of additional vasodilator response with doses of more than 25 mg suggests
that neurohormonal activation might limit the efficacy of high dose of
losartan.
ARTICLES
Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure
Division of Cardiology, University of Maryland School of Medicine, Baltimore 21201.
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