Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms

E. Mironova, N. Boiko, V. Bugaj, V. Kucher, James D Stockand

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Discretionary control of Na(+) excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine-tuned in the aldosterone-sensitive distal nephron by the activity of the epithelial Na(+) channel (ENaC). Here, ENaC functions as a final effector of the renin-angiotensin-aldosterone system (RAAS) during negative feedback control of blood pressure. Mutations affecting ENaC activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na(+) excretion. Recent evidence demonstrates that powerful signalling pathways function in parallel with the RAAS to modulate ENaC activity and blood pressure. An inclusive paradigm is emerging with respect to regulation of blood pressure where ENaC serves as a critical point of convergence for several important signalling systems that affect renal Na(+) excretion. A robust inhibitory purinergic signalling system intrinsic to the distal nephron dynamically regulates ENaC through paracrine ATP signalling via the metabotropic P2Y2 purinergic receptor to properly match urinary Na(+) excretion to dietary Na(+) intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na(+) consumption. Loss of purinergic inhibition of ENaC increases blood pressure by causing inappropriate Na(+) excretion. In contrast, stimulation of the P2Y2 receptor promotes natriuresis and a decrease in blood pressure. Such observations identify purinergic signalling in the distal nephron as possibly causative, when dysfunctional, for certain forms of elevated blood pressure, and as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalActa physiologica (Oxford, England)
Volume213
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Nephrons
Epithelial Sodium Channels
Arterial Pressure
Blood Pressure
Purinergic P2Y2 Receptors
Renin-Angiotensin System
Paracrine Communication
Natriuresis
Aldosterone
Mammals
Reference Values
Salts
Adenosine Triphosphate
Sodium
Mutation

Keywords

  • ENaC/Degenerin
  • hypertension
  • ion channel
  • renin-angiotensin-aldosterone system
  • transport

ASJC Scopus subject areas

  • Physiology

Cite this

Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron : consequences and mechanisms. / Mironova, E.; Boiko, N.; Bugaj, V.; Kucher, V.; Stockand, James D.

In: Acta physiologica (Oxford, England), Vol. 213, No. 1, 01.01.2015, p. 213-221.

Research output: Contribution to journalReview article

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