INCREASED ENDOTHELIN-1 GENE-EXPRESSION IN THE ENDOTHELIUM OF CORONARY-ARTERIES AND ENDOCARDIUM IN THE DOCA-SALT HYPERTENSIVE RAT

Endothelin-1 (ET-1) is a potent vasoconstrictor and inotropic agent which may also induce cell hypertrophy, The role of ET-1 in ventricular hypertrophy in hypertension is unknown. We investigated ET-1 gene expression and immunoreactive ET-1 (ir-ET-l) concentration in the heart of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. To identify the cellular sites of ET-1 production in the heart, we performed in situ hybridization histochemistry. DOCA-treated rats which underwent unilateral nephrectomy (Uni-Nx) or not, exhibited mild systolic blood pressure elevation and ventricular hypertrophy. Blood pressure elevation and cardiac hypertrophy were more severe in DOCA-salt hypertensive rats, Ventricular ET-1 mRNA was similar in Uni-Nx control and DOCA-treated rats by Northern blot analysis, whereas in DOCA-salt hypertensive rats it was significantly increased. Ir-ET-1 concentration was also enhanced in ventricles from DOCA-salt hypertensive rats compared with Uni-Nx control rats. In situ hybridization histochemistry using a S-35-labelled complementary RNA ET-1 probe demonstrated that the level of ET-1 mRNA transcripts was increased exclusively in endothelial cells of large epicardial and small intramyocardial coronary arteries and in areas of the endocardium, but not significantly in myocardial cells of either the atria or ventricles, Enhanced ET-1 production may contribute to vascular changes, both structural and functional, in the heart in this model of hypertension in the rat, but probably does not contribute to the severe cardiac hypertrophy found in DOCA-salt hypertensive rats. (C) 1995 Academic Press Limited