Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure.
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.


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.
Gottlieb
S S
SS
Division of Cardiology, University of Maryland School of Medicine, Baltimore 21201.
Dickstein
K
K
Fleck
E
E
Kostis
J
J
Levine
T B
TB
LeJemtel
T
T
DeKock
M
M
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan; D009638:Norepinephrine