Beneficial cardiovascular effects of endothelin ET(A) receptor blockade in established long-term heart failure after myocardial infarction.
Although experimental prevention studies have suggested therapeutic potential of endothelin (ET) antagonists for the treatment of heart failure, the results of clinical trials using ET antagonists on top of standard heart failure medications have been largely disappointing. This experimental study investigated the effects of chronic ET(A) receptor blockade in long-term survivors of myocardial infarction who had developed stable chronic heart failure in the absence of other treatments. Systolic blood pressure, heart rate, organ weights of the right atrium and ventricle, and the lungs were determined, and tissue ET-1 peptide levels were measured in cardiac tissue, lung, and aorta. The results show that chronic blockade of ET(A) receptors stabilizes systolic blood pressure and reverses the heart failure-induced weight increases of right heart chambers and lung. The changes observed occurred independently of tissue ET-1 concentrations and heart rate, suggesting mechanisms independent of local cardiac or pulmonary ET-1 synthesis, which are yet to be identified.
Vetter
Diana
D
Medizinische Poliklinik, Universitätsspital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
Shaw
Sidney G
SG
Brandes
Ralf P
RP
Münter
Klaus
K
Vetter
Wilhelm
W
Barton
Matthias
M
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D065130:Endothelin A Receptor Antagonists; D006325:Heart Atria / Q000254:growth & development*; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000254:growth & development*; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D065130:Endothelin A Receptor Antagonists