Estrogen regulates adrenal angiotensin type 1 receptors by modulating adrenal angiotensin levels.
Estrogen inhibits adrenal angiotensin type 1 receptor (AT(1)R) binding sites and attenuates the adrenal responsivity to angiotensin II (Ang II). Ang II modulates AT(1)R expression. Here, we determined if estrogen-induced down-regulation of adrenal AT(1)Rs involves modulation of adrenal Ang II. Female rats were ovariectomized (OVX) and injected with 17beta-estradiol benzoate (E(2); 40 micro g/kg) or vehicle for 7 d. Adrenal Ang II was separated from other angiotensin peptides by HPLC and measured by RIA. Scatchard analysis of radioligand binding curves showed that E(2) or captopril (Cap; 0.5 g/liter water) significantly reduced adrenal AT(1)R binding (maximum binding capacity) by 22% and 19%, respectively, compared with OVX (276 +/- 2.09 fmol/mg protein). E(2) and Cap lowered adrenal Ang II levels by 39% and 21%, respectively, compared with OVX (4.10 +/- 0.44 pmol/g). E(2) caused no further reductions in adrenal AT(1)R binding or in Ang II levels in Cap-treated OVX rats. High-dose Ang II infusion (1000 ng/kg.min) increased adrenal Ang II levels by 71% and lowered AT(1)R binding by 18%. Under these infusion conditions, E(2) did not reduce adrenal Ang II or AT(1)R binding. No differences in AT(1)R affinity (dissociation constant) were observed among groups. These data suggest that E(2) regulates the number of adrenal AT(1)R binding sites indirectly by modulating adrenal Ang II.
Wu
Zheng
Z
Department of Physiology, Georgetown University, Washington, DC 20057, USA.
Zheng
Wei
W
Sandberg
Kathryn
K
D000311:Adrenal Glands / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism
D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004958:Estradiol; D002216:Captopril