ROLE OF ENDOTHELIN RECEPTOR SUBTYPES IN THE IN-VIVO REGULATION OF RENAL-FUNCTION

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ET(A) and ET(B) receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg(-1).min(-1)) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 mu g kg(-1) min(-1)), a selective ET(A) antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ET(B) receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ET(A) receptor contributes to the renal vasoconstriction, whereas the ET(B) receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ET(A) or ET(B) receptor activation.