Endothelin A Receptor Antagonism in Experimental Congestive Heart Failure Results in Augmentation of the Renin-Angiotensin System and Sustained Sodium Retention
Key result
In a canine model of congestive heart failure, 7 days of ET-A receptor antagonism with LU135252 did not improve sodium excretion and increased plasma renin activity and ET-1 levels.
Why the study?
Does chronic oral ET-A receptor antagonism improve sodium excretion and neurohumoral function in a canine model of pacing-induced congestive heart failure?
Population
Canine model of progressive left ventricular dysfunction (pacing-induced congestive heart failure), n=13
Comparison
Chronic oral ET-A receptor antagonism for 7 days vs Untreated congestive heart failure
Design
Preclinical
Follow-up
7 days
Authors
Discussion
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Member takes
Implication
ET-A antagonism may worsen neurohormonal activation without natriuresis in heart failure; leaves open optimal endothelin pathway targeting in clinical trials.
Structured PICO
Does chronic oral ET-A receptor antagonism improve sodium excretion and neurohumoral function in a canine model of pacing-induced congestive heart failure?
P
Population
Canine model of progressive left ventricular dysfunction (pacing-induced congestive heart failure), n=13
I
Intervention
Chronic oral ET-A receptor antagonism (LU135252) for 7 days
C
Comparator
Untreated congestive heart failure
O
Outcome
Neurohumoral function, renal hemodynamics, and sodium excretionsurrogate
In a canine model of CHF, ET-A receptor antagonism increased plasma renin activity and ET-1 without improving sodium excretion, offering a potential mechanism for worsening symptoms observed in clinical trials.
Cite This Study
Schirger et al. (2003) studied Congestive heart failure (n=13). ET-A receptor antagonism (LU135252) vs. Untreated CHF was evaluated on Sodium excretion, neurohumoral function, and renal hemodynamics. In a canine model of congestive heart failure, 7 days of ET-A receptor antagonism with LU135252 did not improve sodium excretion and increased plasma renin activity and ET-1 levels.