CHARACTERIZATION OF CANINE RENAL ENDOTHELIN RECEPTOR SUBTYPES AND THEIR FUNCTION

Binding and renal functional studies were conducted to characterize en dothelin (ET) receptors in the dog kidney. Binding studies that were p erformed in renal cortical membranes by using [I-125]-ET-1 and [I-125] -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, reve aled that the ratios of ET(A) to ET(B) receptors in cortical, medullar y and papillary membranes were 22:78, 39:61 and 50:50, respectively. I n 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 filtratio n rate(GFR). At a dose of 10 ng kg(-1) min(-1) of ET-1, RBF and GFR de creased 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 signific ant inhibition of the ET-l-induced renal vasoconstriction. At identica l doses as ET-I, S6c had little effect on either RBF (-3 +/- 6%) or GF R (-6 +/- 16%). ET-1 decreased urine Row and had little effect on frac tional sodium excretion, whereas S6c increased both urine flow and fra ctional sodium excretion. These data indicate that ET-l-induced renal vasoconstriction in the dog is mediated by ET(A) receptors; however, E T(B) receptor stimulation may inhibit sodium reabsorption.