Intrinsic control of sodium excretion in the distal nephron by inhibitory purinergic regulation of the epithelial Na + channel

Research output: Contribution to journalReview article

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Abstract

Purpose of Review: This review summarizes the new evidence for an intrinsic control system in the aldosterone-sensitive distal nephron in which purinergic signaling regulates sodium transport and governs renal sodium excretion. Recent Findings: Electrophysiological studies identify epithelial Na + channels (ENaC) as final effectors of purinergic signaling via P2Y 2 receptors in the distal nephron. Inhibition of ENaC by autocrine/paracrine purinergic signaling reduces sodium reabsorption allowing an appropriately graded pressure-natriuresis response when delivery of sodium to the distal nephron is high. Disruption of this intrinsic control mechanism decreases sodium excretion and therefore has a prohypertensive effect. Because purinergic inhibition of ENaC is tonic yet submaximal, its enhancement increases sodium excretion and therefore has an antihypertensive action. Summary: Purinergic inhibitory regulation of ENaC is a key component of an intrinsic control system that enables the distal nephron to respond appropriately to the delivered load of sodium. This control system is physiologically important and functions in parallel with extrinsic control by the renin-angiotensin-aldosterone system, enabling sodium excretion to keep pace with sodium intake, especially when intake is high, and thereby maintaining arterial blood pressure. Disruption of intrinsic control of sodium transport by the distal nephron likely contributes to diseases such as arterial hypertension.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalCurrent opinion in nephrology and hypertension
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2012

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Keywords

  • ATP
  • ENaC
  • P2Y
  • hypertension
  • sodium transport

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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