In vivo stimulation of aldosterone biosynthesis by endothelin: loci of action and effects of doses and infusion rate.
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.
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
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A
Pecci
C E
CE
Gomez-Sanchez
M E
ME
de Bedners
C P
CP
Lantos
E N
EN
Cozza
D000450:Aldosterone / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril