Possible involvement of endothelin-1 in cardiac hypertrophy.

In an attempt to ascertain a possible involvement of endothelin-1 (ET-1) in the development of cardiac hypertrophy induced by hemodynamic overloads in vivo, the expression of prepro ET-1 mRNA in the cardiac tissue and the plasma level of ET-1 were determined in rats undergoing various treatments for inducing cardiac hypertrophy. One week after aortic banding (AB), the rat exhibited left ventricular hypertrophy characterized by ventricular wall thickening, i.e. concentric hypertrophy. In contrast, the aortic regurgitation (AR) produced left ventricular enlargement without wall thickening 1 week after the operation, i.e. eccentric hypertrophy. Monocrotaline treatment (s.c.) also caused marked hypertrophy in the right ventricle (concentric hypertrophy) 3 weeks later, which was accompanied by a severe pulmonary hypertension (MCT-PH). A Northern blot analysis revealed that AB and MCT-PH markedly increased the expression of prepro ET-1 mRNA in the left and right ventricles, respectively. The rats with MCT-PH but not with AB displayed a significant higher level in their plasma ET-1 levels compared with control animals. In contrast, the rats undergoing AR surgery exhibited no significant elevation in either prepro ET-1 mRNA in the heart or the plasma ET-1 concentration. The results of the present study suggest that ET-1 is involved at least in part in the development of concentric but probably not eccentric cardiac hypertrophy induced by hemodynamic overloads.