Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats.
To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (AII) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma AII levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to AII; an increase by 4 orders of magnitude in the threshold dose for AII and a decrease in the maximum AII-stimulated level. The maximum AII-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsiveness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells, involving the specific receptors and the aldosterone biosynthesis, to AII.
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018161:Receptors, Mineralocorticoid
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D006493:Heparin; D011188:Potassium; D003345:Corticosterone