The effect of angiotensin II and saralasin on 18-hydroxy-11-deoxycorticosterone production by isolated human adrenal glomerulosa cells.
To assess the role of angiotensin II (AII) in regulating 18-hydroxy-11-deoxycorticosterone (18-OHDOC) secretion in man, isolated human adrenal glomerulosa cells were incubated with AII and/or its competitive antagonist, saralasin. AII 2.4 X 10(-8) M) elicited an 80% increase in 18-OHDOC levels as well as similar increases in aldosterone, 18-hydroxycorticosterone, and corticosterone (P less than 0.01). Saralasin (10(-8) M) caused a partial but significant inhibition of AII-stimulated 18-OHDOC production, while 10(-6) M saralasin blocked AII-stimulated steroidogenesis completely. In addition, both concentrations of saralasin caused 10--30% decrements in basal steroid levels. The direct AII effect on 18-OHDOC secretion and the antagonistic effect of saralasin on both exogenous and endogenous AII-stimulated steroidogenesis, documented in these experiments, indicate that the increase in 18-OHDOC levels after sodium restriction reported in man is probably mediated by the renin-angiotensin system. Furthermore, because high concentrations of saralasin did not increase aldosterone secretion, the partial agonist properties of saralasin in vivo in man may not be due to a direct effect on the glomerulosa cell.
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D015070:18-Hydroxydesoxycorticosterone / Q000378:metabolism*; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000601:surgery; D003345:Corticosterone / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D012504:Saralasin / Q000494:pharmacology*
D015070:18-Hydroxydesoxycorticosterone; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D012504:Saralasin; D003345:Corticosterone