Abstract

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 ETA- and ETB-selective ligands, BQ123 (cyclo [D-Trp-D-Asp-L-Pro-D-Val-L-Leu]) and sarafotoxin 6c (S6c), respectively, revealed that the ratios of ETA to ETB 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 micrograms 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 ETA receptors; however, ETB receptor stimulation may inhibit sodium reabsorption.