Upregulation of endothelin B receptors in kidneys of DOCA-salt hypertensive rats

被引:58
作者
Pollock, DM [1 ]
Allcock, GH
Krishnan, A
Dayton, BD
Pollock, JS
机构
[1] Med Coll Georgia, Vasc Biol Ctr, Dept Surg, Augusta, GA 30912 USA
[2] Med Coll Georgia, Vasc Biol Ctr, Dept Physiol & Endocrinol, Augusta, GA 30912 USA
[3] Med Coll Georgia, Vasc Biol Ctr, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA
[4] Abbott Labs, Pharmaceut Discovery, Abbott Pk, IL 60064 USA
关键词
endothelin B receptors; deoxycorticosterone; hypertension; sodium diet;
D O I
10.1152/ajprenal.2000.278.2.F279
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Experiments were designed to elucidate the role of endothelin B receptors (ET(B)) on arterial pressure and renal function in deoxycorticosterone acetate (DOCA)salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy and were treated with either DOCA and salt (0.9% NaCl to drink) or placebo. DOCA-salt rats given the ET(B)-selective antagonist, A-192621, for 1 wk (10 mg.kg(-1) day-l in the food) had significantly greater systolic arterial pressure compared with untreated DOCA-salt rats (208 +/- 7 vs. 182 +/- 4 mmHg) whereas pressure in placebo rats was unchanged. In DOCA-salt, but not placebo rats, A-192621 significantly decreased sodium and water excretion along with parallel decreases in food and water intake. To determine whether the response in DOCA-salt rats was due to increased expression of ETB receptors, endothelin receptor binding was performed by using membranes from renal medulla. Maximum binding (B,,) of [(125)I]ET-1, [125I]ET-3, and [(125)I]IRL-1620 increased from 227 +/- 42, 146 +/- 28, and 21 +/- 1 fmol/mg protein, respectively, in placebo rats to 335 +/- 27, 300 +/- 38, and 61 +/- 6 fmol/mg protein, respectively, in DOCA-salt hypertensive rats. The fraction of receptors that are the ETB subtype was significantly increased in DOCA-salt (0.88 +/- 0.07) compared with placebo (0.64 +/- 0.01). The difference between [(125)I]ET-3 and [(125)I]IRL-1620 binding is consistent with possible ETB receptor subtypes in the kidney. These results indicate that ETB receptors in the renal medulla are up-regulated in the DOCA-salt hypertensive rat and may serve to maintain a lower arterial pressure by promoting salt and water excretion.
引用
收藏
页码:F279 / F286
页数:8
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