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

Experiments were designed to elucidate the role of endothelin B receptors ( ETB) on arterial pressure and renal function in deoxycorticosterone acetate (DOCA)salt hypertensive rats. Male Sprague-Dawley rats underwent uninephre ctomy and were treated with either DOCA and salt (0.9% NaCl to drink) or pl acebo. DOCA-salt rats given the ETB-selective antagonist, A-192621, for 1 w k (10 mg.kg(-1) day-l in the food) had significantly greater systolic arter ial pressure compared with untreated DOCA-salt rats (208 +/- 7 vs. 182 +/- 4 mmHg) whereas pressure in placebo rats was unchanged. In DOCA-salt, but n ot placebo rats, A-192621 significantly decreased sodium and water excretio n along with parallel decreases in food and water intake. To determine whet her the response in DOCA-salt rats was due to increased expression of ETB r eceptors, endothelin receptor binding was performed by using membranes from renal medulla. Maximum binding (B,,) of [I-125]ET-1, [125I]ET-3, and [I-12 5]IRL-1620 increased from 227 +/- 42, 146 +/- 28, and 21 +/- 1 fmol/mg prot ein, 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 [I-125]ET-3 and [I-125]IRL-1620 binding is consistent with possible ETB receptor subtypes in the kidney. These results indicate that ETB recep tors in the renal medulla are up-regulated in the DOCA-salt hypertensive ra t and may serve to maintain a lower arterial pressure by promoting salt and water excretion.