Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production

Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and pr...

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Bibliographic Details
Published inThe American journal of physiology Vol. 265; no. 2 Pt 1; p. E179
Main Authors Cozza, E N, Gomez-Sanchez, C E
Format Journal Article
LanguageEnglish
Published United States 01.08.1993
Subjects
Aldosterone - biosynthesis
Angiotensin II - pharmacology
Animals
Calcium - physiology
Cells, Cultured
Drug Synergism
Endothelins - pharmacology
Protein Kinase C - physiology
Zona Glomerulosa - cytology
Zona Glomerulosa - metabolism
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Summary:Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC.
ISSN:0002-9513
DOI:10.1152/ajpendo.1993.265.2.E179