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
相关论文
共 38 条
[1]   ETA receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats [J].
Allcock, GH ;
Venema, RC ;
Pollock, DM .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1998, 275 (01) :R245-R252
[2]   ANTIHYPERTENSIVE EFFECTS OF A NOVEL ENDOTHELIN-A RECEPTOR ANTAGONIST IN RATS [J].
BIRD, JE ;
MORELAND, S ;
WALDRON, TL ;
POWELL, JR .
HYPERTENSION, 1995, 25 (06) :1191-1195
[3]  
BROOKS DP, 1995, J CARDIOVASC PHARM, V26, pS322
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]   The role of ET(B) receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ET(B) receptor antagonist Ro 46-8443 [J].
Clozel, M ;
Breu, V .
FEBS LETTERS, 1996, 383 (1-2) :42-45
[6]   IN-SITU HYBRIDIZATION SHOWS INCREASED ENDOTHELIN-1 MESSENGER-RNA LEVELS IN ENDOTHELIAL-CELLS OF BLOOD-VESSELS OF DEOXYCORTICOSTERONE ACETATE-SALT HYPERTENSIVE RATS [J].
DAY, R ;
LARIVIERE, R ;
SCHIFFRIN, EL .
AMERICAN JOURNAL OF HYPERTENSION, 1995, 8 (03) :294-300
[7]   Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labelling [J].
Dean, R ;
Zhuo, JL ;
Alcorn, D ;
Casley, D ;
Mendelsohn, FAO .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1996, 23 (6-7) :524-531
[8]  
DENUCCI G, 1988, P NATL ACAD SCI USA, V85, P9797
[9]  
EDWARDS RM, 1993, J PHARMACOL EXP THER, V267, P1028
[10]   Localization of endothelin ET(A) and ET(B) receptor-mediated constriction in the renal microcirculation of rats [J].
Endlich, K ;
Hoffend, J ;
Steinhausen, M .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 497 (01) :211-218