Differential regulation of ET_A and ET_B in the renal tissue of rats with compensated and decompensated heart failure

Endothelin-1 (ET-1) exerts its biological actions through two receptor subtypes: endothelin-A (ET_A) receptor and endothelin-B (ET _B) receptor. We demonstrated previously that ET-1 induces systemic and renal cortical vasoconstriction via ET_A whereas ET_B mediates medullary vasodilation. Congestive heart failure (CHF) is characterized by increased vascular resistance and impaired renal hemodynamic and excretory function. While the pathophysiological effects of ET-1 in CHF are well established, the status of ET_A and ET_B in the kidney is poorly characterized. The present study examined the immunostaining and localization of ET_A and ET_B in the renal cortex and medulla of rats with experimental CHF induced by aorto-caval fistula. Rats with CHF were further subdivided, based on their daily urinary sodium excretion, into rats with compensated (urinary sodium excretion > 1200 μEq/day) and decompensated CHF (urinary sodium excretion < 200 μEq/day). ET_A is predominantly localized to the cortex mainly in the peritubular capillaries, and is upregulated in rats with compensated and decompensated CHF compared with sham controls. In contrast, ET_B is preferentially expressed in the outer and inner medulla, mainly in the vasa recta, the thick ascending limb of Henle's loop and the collecting duct. While compensated CHF is associated with upregulation of ET_B in the collecting duct and vasa recta, decompensated CHF is accompanied with enhanced ET_B abundance in the vasa recta and remarkable downregulation of this receptor subtype in the collecting duct. The findings suggest that upregulation of ET_A may lead to a decrease in cortical blood flow while upregulation of ET_B in the vasa recta probably contributes to the preservation of medullary blood flow. Furthermore, downregulation of ET_B in the collecting duct, only in rats with decompensated CHF, could contribute to sodium retention in that subgroup.