Demonstration of an angiotensin II-induced negative feedback effect on aldosterone synthesis in isolated rat adrenal zona glomerulosa cells.
Although both angiotensin II (Ang II) and potassium ion (K+) induce marked elevations of cytosolic free calcium concentration, [Ca2+]c, in adrenal zona glomerulosa cells-an effect which is thought to trigger aldosterone synthesis-Ang II is also known to reduce the sustained [Ca2+]c rise induced by K+. We have examined whether this effect of Ang II on the calcium messenger system is reflected at the level of the final biological response, aldosterone synthesis. In superfused isolated rat glomerulosa cells, K+ (8 mM) induced a sustained, 60-fold increase in aldosterone production. In contrast, the maximal response to Ang II (10 nM) amounted to only 10 times the basal production. When added subsequent to K+ stimulation, Ang II provoked an immediate and dramatic drop in aldosterone synthesis, to levels obtained with Ang II alone. Under conditions of maximal K+ stimulation, this effect depended upon Ang II concentration, while the well-known synergistic effect was observed with submaximal concentrations of both agonists. The inhibitory effect of Ang II could be reproduced with dioctanoylglycerol, a selective activator of protein kinase C. By contrast, the aldosterone response to adrenocorticotropic hormone (ACTH) was not affected by Ang II. At submaximal concentrations of ACTH, the steroidogenic effect of Ang II was even additive to that of ACTH. Thus, we have shown that, under conditions of maximal stimulation, Ang II exerts a profound inhibition of steroidogenesis in K(+)-stimulated rat adrenal glomerulosa cells. This counter-regulatory mechanism may ensure adequate levels of aldosterone production in vivo.
Aptel
H B
HB
Division of Endocrinology and Diabetology, University Hospital, Geneva, Switzerland.
Johnson
E I
EI
Vallotton
M B
MB
Rossier
M F
MF
Capponi
A M
AM
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D011188:Potassium