Intracellular pH in the resistance vasculature: regulation and functional implications

J Vasc Res. 2012;49(6):479-96. doi: 10.1159/000341235. Epub 2012 Aug 18.


Net acid extrusion from vascular smooth muscle (VSMCs) and endothelial cells (ECs) in the wall of resistance arteries is mediated by the Na(+),HCO(3)(-) cotransporter NBCn1 (SLC4A7) and the Na(+)/H(+) exchanger NHE1 (SLC9A1) and is essential for intracellular pH (pH(i)) control. Experimental evidence suggests that the pH(i) of VSMCs and ECs modulates both vasocontractile and vasodilatory functions in resistance arteries with implications for blood pressure regulation. The connection between disturbed pH(i) and altered cardiovascular function has been substantiated by a genome-wide association study showing a link between NBCn1 and human hypertension. On this basis, we here review the current evidence regarding (a) molecular mechanisms involved in pH(i) control in VSMCs and ECs of resistance arteries at rest and during contractions, (b) implications of disturbed pH(i) for resistance artery function, and (c) involvement of disturbed pH(i) in the pathogenesis of vascular disease. The current evidence clearly implies that pH(i) of VSMCs and ECs modulates vascular function and suggests that disturbed pH(i) either consequent to disturbed regulation or due to metabolic challenges needs to be taken into consideration as a mechanistic component of artery dysfunction and disturbed blood pressure regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid-Base Equilibrium / physiology
  • Animals
  • Arteries / physiology
  • Blood Pressure / physiology
  • Endothelial Cells / metabolism*
  • Humans
  • Hydrogen-Ion Concentration*
  • Hypertension / physiopathology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Reperfusion Injury / physiopathology
  • Sodium-Bicarbonate Symporters / physiology
  • Sodium-Hydrogen Exchangers / physiology


  • Sodium-Bicarbonate Symporters
  • Sodium-Hydrogen Exchangers