Pathological pressure overload from monocrotaline-induced pulmonary hypertension markedly increased gene expression of ET-1, ET(A) receptor, and ET(B) receptor in the right ventricle of rats.
Pathological pressure overload, such as in pulmonary hypertension, enhances myocardial ET-1 system gene expression, whereas physiological pressure differences do not.
Endothelin (ET)-1 has potent positive inotropic and chronotropic activity in the heart and induces cardiac hypertrophy. The production of ET-1 in the heart is reported to be increased under some conditions. In normal circulation, the pressure load to the left ventricle (LV) is much greater than that to the right ventricle (RV). In this study, we investigated the gene expression of the myocardial ET-1 system (ET-1, ET(A) receptor, and ET(B) receptor) in the RV and LV of normal rats and also investigated these genes in hypertrophied RV due to pathological pulmonary hypertension (PH). Normal rats showed no differences between the RV and LV in the gene expression of either ET-1, ET(A) receptor, or ET(B) receptor in either the adult stage (11 wk old) or the neonatal stage (1 and 8 days old). On the other hand, the expression of both atrial natriuretic peptide (ANP) mRNA and B-type natriuretic peptide (BNP) mRNA was significantly greater in the LV than in the RV in adult rats. Gene expression of ET-1, ET(A) receptor, and ET(B) receptor in the RV was markedly higher in rats with monocrotaline-induced (pathological) PH than that in control rats. The expression of ANP mRNA and BNP mRNA in the RV was also markedly higher in the rats with PH. In conclusion, the data suggest that gene expression of the ET-1 system in the myocardium is not affected by physiological pressure load in either the adult stage or neonatal stage; however, it is enhanced by pathological pressure overload such as that in PH.
Ueno et al. (Mon,) conducted a other in Pulmonary hypertension. Monocrotaline-induced pulmonary hypertension (pathological pressure overload) vs. Normal control rats (physiological pressure load) was evaluated on Gene expression of the myocardial ET-1 system (ET-1, ET(A) receptor, and ET(B) receptor). Pathological pressure overload from monocrotaline-induced pulmonary hypertension markedly increased gene expression of ET-1, ET(A) receptor, and ET(B) receptor in the right ventricle of rats.