Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-, and potassium-stimulated aldosterone secretion.
The zona glomerulosa cells of the adrenal gland have an intrinsic renin-angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells. Zona glomerulosa cells were cultured in PFMR-4 medium containing 10% fetal calf serum for 72 hours, and the medium was replaced with serum-free medium for the next 24-hour experimental period. DuP 753 (10 mumol/L) inhibited basal aldosterone secretion (from 88.6 +/- 7.1 to 54.8 +/- 9.6 pg/10(6) cells per hour; 38% inhibition). EXP 3174, an active metabolite of DuP 753, also inhibited aldosterone dose dependently (from 88.6 +/- 7.1 to 55.9 +/- 8.4 at 1 mumol/L and 88.6 +/- 7.1 to 21.7 +/- 3.3 at 100 mumol/L; 37% and 75% inhibition, respectively). Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition). DuP 753 inhibited Ang II (100 nmol/L)-stimulated aldosterone production in a dose-dependent fashion, with a 30% reduction at 100 nmol/L and complete inhibition at 100 mumol/L. DuP 753 also inhibited potassium (12 nmol/L) and corticotropin (1 nmol/L) stimulation of aldosterone in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Gupta
P
P
Department of Medicine, Medical College of Ohio, Toledo 43699-0008.
Franco-Saenz
R
R
Mulrow
P J
PJ
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D011188:Potassium