Invivo Stimulation of Aldosterone Biosynthesis by Endothelin - Loci of Action and Effects of Doses and Infusion Rate

PECCI, A; GOMEZSANCHEZ, CE; DEBEDNERS, MEO; LANTOS, CP; COZZA, EN; ADALI PECCI

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

ELSEVIER IRELAND LTD

Año: 1993 vol. 45 p. 555 - 561

0960-0760

Infusion of endothelin-1 (ET-1) into rats increased adrenal mitochondrial synthesis of aldosterone from deoxycorticosterone and the adrenal cytosolic content of aldosterone. The dose-response relationships for these last two effects of ET-1 were found to be biphasic with a maximum (corresponding to 80 to 200% increase) at 50 to 80 ng ET-1/kg/min, and were also dependent on the infusion rate. Plasma aldosterone levels were also increased in a similar ratio. Previous infusion of the converting enzyme inhibitor enalapril did not affect the ET-1-induced increase in steroidogenesis. Finally, pregnenolene production was also increased in incubations of mitochondria from treated rats. These results indicate that ET-1 augments aldosteronogenesis by increasing the early as well as the late pathway. These effects were independent of the formation of angiotensin II. Isolated glomerulosa cells responded to ET-1 increasing aldosterone production in a dose-related fashion. These results confirm a direct effect of ET-1 on the adrenal gland in vivo.