Characterization of canine renal endothelin receptor subtypes and their function
Brooks, D.P.; DePalma, P.D.; Pullen, M.; Nambi, P.
Journal of Pharmacology and Experimental Therapeutics 268(3): 1091-1097
1994
ISSN/ISBN: 0022-3565 PMID: 8138922 Document Number: 437413
Binding and renal functional studies were conducted to characterize endothelin (ET) receptors in the dog kidney. Binding studies that were performed in renal cortical membranes by using (125I)-ET-1 and (125I)-ET-3 and the ET-A- and ET-B-selective ligands, BQ123 (cyclo (D-Trp-D-Asp-L-PrO-D-Val-L-Leu)) and sarafotoxin 6c (S6c), respectively, revealed that the ratios of ET-A to ET-B receptors in cortical, medullary and papillary membranes were 22:78, 39:61 and 50:50, respectively. In vivo studies in the anesthetized dog demonstrated that an intrarenal artery infusion of ET-1 (0.3-10 ng kg-1 min-1) resulted in a dose-dependent decrease in renal blood flow (RBF) and glomerular filtration rate (GFR). At a dose of 10 ng kg-1 min-1 of ET-1, RBF and GFR decreased by 82 +- 6% and 89 +- 6%, respectively. An infusion of BQ123 (10 mu-g kg-1 min-1) into the renal artery resulted in a significant inhibition of the ET-1-induced renal vasoconstriction. At identical doses as ET-1, S6c had little effect on either RBF (-3 +- 6%) or GFR (-6 +- 16%). ET-1 decreased urine flow and had little effect on fractional sodium excretion, whereas S6c increased both urine flow and fractional sodium excretion. These data indicate that ET-1 -induced renal vasoconstriction in the dog is mediated by ET-A receptors; however, ET-B receptor stimulation may inhibit sodium reabsorption.