Differential regulation of angiotensin II receptor subtypes in the adrenal gland: role of aldosterone.
It has been shown that aldosterone potentiates the action of angiotensin II (Ang II) in cultured rat vascular smooth muscle cells solely by increasing the number of Ang II receptors. The mechanisms responsible for aldosterone-Ang II interactions in the adrenal gland are unknown. The present study was designed to investigate the effect of aldosterone on expression of Ang II receptor subtypes (AT1 and AT2) in the adrenal gland. Seven-week-old male Wistar rats were treated for 2 weeks with either aldosterone (0.05 microg/h, n=14) or vehicle (n=14) by use of implanted osmotic minipumps. Systolic blood pressure was not altered by aldosterone treatment. Plasma aldosterone levels were higher in aldosterone-treated rats (181+/-53 pg/mL) compared with vehicle-treated rats (33+/-21 pg/mL, P<0.05). Northern blot analysis and radioligand binding assay showed that adrenal AT1 mRNA levels and AT1 receptor density in aldosterone-treated rats were not statistically different from those of vehicle-treated rats. However, immunohistochemical studies showed that the highest adrenal AT1 receptor expression was shifted from the zona glomerulosa to the zona fasciculata after aldosterone treatment. In contrast, adrenal AT2 mRNA and AT2 receptor density in aldosterone-treated rats were decreased by approximately 50% and 40%, respectively, compared with vehicle-treated rats (P<0.05). Aldosterone-induced decrease in adrenal AT2 receptor expression occurred mainly in the medulla. Thus, aldosterone differentially modulates the expression of AT1 and AT2 receptors in the adrenal gland. Although the function of the AT2 receptor in the adrenal gland is largely unknown, our data indicate that aldosterone may modulate the effect of Ang II by altering the location of AT1 receptors and by reducing the number of AT2 receptors in the adrenal gland.
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1065, USA. dwang@utmb.edu
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D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D000804:Angiotensin II / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D003627:Data Interpretation, Statistical; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics*; D013194:Staining and Labeling
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone