Differential regulation of ETA and ETB in the renal tissue of rats with compensated and decompensated heart failure

Bahaa N. Francis, Zaid Abassi, Samuel Heyman, Joseph Winaver, Aaron Hoffman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Endothelin-1 (ET-1) exerts its biological actions through two receptor subtypes: endothelin-A (ETA) receptor and endothelin-B (ET B) receptor. We demonstrated previously that ET-1 induces systemic and renal cortical vasoconstriction via ETA whereas ETB 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 ETA and ETB in the kidney is poorly characterized. The present study examined the immunostaining and localization of ETA and ETB 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). ETA 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, ETB 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 ETB in the collecting duct and vasa recta, decompensated CHF is accompanied with enhanced ETB abundance in the vasa recta and remarkable downregulation of this receptor subtype in the collecting duct. The findings suggest that upregulation of ETA may lead to a decrease in cortical blood flow while upregulation of ETB in the vasa recta probably contributes to the preservation of medullary blood flow. Furthermore, downregulation of ETB in the collecting duct, only in rats with decompensated CHF, could contribute to sodium retention in that subgroup.

Original languageEnglish
Pages (from-to)S362-S365
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Nov 2004
Externally publishedYes

Keywords

  • Endothelin
  • Endothelin receptors
  • Heart failure
  • Kidney
  • Rat

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