INDUCTION OF IMMEDIATE-EARLY GENES BY ANGIOTENSIN-H AND ENDOTHELIN-1 IN ADULT-RAT CARDIOMYOCYTES

Objective: Few molecular signals for induction of myocardial hypertrop hy have been identified. This study was carried out to investigate the action of angiotensin II and endothelin on the growth- and differenti ation-related genes Egr-1 (early growth response gene 1) and c-fos in isolated adult rat cardiomyocytes. Methods: Cardiac myocytes from male Wistar-Kyoto rats were isolated and incubated with angiotensin II and endothelin-1 in Dulbecco's modified Eagle's medium. RNA was isolated and blotted, and densitometric analysis was performed. All experiments were repeated at least three times. Results: Endothelin-1 (10(-7) mmo l/1) induced a 20-25-fold rise in Egr-1 messenger RNA within 15 min. T his effect was dose-dependent. c-fos was induced 10-20-fold within 15 min with similar dose-response characteristics. Angiotensin II also in duced Egr-1 and c-fos with kinetics similar to endothelin but a cofact or from fetal calf serum was needed for full c-fos expression. The pro tein kinase C activator phorbol 12-myristate 13-acetate also induced E gr-1. Conclusions: The results identify Egr-1 and c-fos as target gene s for the action of endothelin and angiotensin II in the adult myocard ium suggesting that induction of the genes may be part of the signal t ransduction pathway for angiotensin II and endothelin in the myocardiu m.