Endothelin-1 in heart and pulmonary tissue in experimental heart failure.

We studied the effect of congestive heart failure (CHF) on the tissue levels of endothelin 1 (ET-1) and of the mRNA of prepro-ET-1 in the rat. Congestive heart failure was produced by ligation of the left coronary artery. The rats were killed 3 weeks after the ligation. Congestive heart failure was determined by elevated plasma atrial natriuretic peptide and by a myocardial infarction scar covering more than 30% of the left ventricular circumference. Both ET-1 and prepro-ET-1 mRNA were measured in cardiac ventricles and lungs by radioimmunoassay and quantitative polymerase chain reaction. The rats with CHF had an increased heart weight/body weight ratio and elevated plasma atrial natriuretic peptide levels. In rats with CHF, as compared to controls, the concentration of ET-1 was elevated 3.6-fold in pulmonary tissue and 1.4-fold in the right ventricle, respectively, but not in the left ventricle. The concentration of mRNA showed a similar pattern, but due to methodological limitations this was assumed to represent a rough estimate only. The enhanced production of ET-1 in the right ventricle and in the pulmonary tissue may be of pathophysiological importance for the development of high pulmonary vascular resistance in CHF.