Transient Receptor Potential Vanilloid-1 Channels Contribute to the Regulation of Acid- and Base-Induced Vasomotor Responses

J Vasc Res. 2016;53(5-6):279-290. doi: 10.1159/000452414. Epub 2016 Dec 7.

Abstract

pH changes can influence local blood flow, but the mechanisms of how acids and bases affect vascular tone is not fully clarified. Transient receptor potential vanilloid-1 (TRPV1) channels are expressed in vessels and can be activated by pH alterations. Thus, we hypothesized that TRPV1 channels are involved in the mediation of vascular responses to acid-base changes. Vasomotor responses to HCl, NaOH, and capsaicin were measured in isolated murine carotid and tail skin arteries. The function of TRPV1 was blocked by either of three approaches: Trpv1 gene disruption, pharmacological blockade with a TRPV1 antagonist (BCTC), and functional impairment of mainly neural TRPV1 channels (desensitization). In each artery type of control mice, HCl caused relaxation but NaOH contraction, and both responses were augmented after genetic or pharmacological TRPV1 blockade. In arteries of TRPV1-desensitized mice, HCl-induced relaxation did not differ from controls, whereas NaOH-induced contraction was augmented. All three types of TRPV1 blockade had more pronounced effects in carotid than in tail skin arteries. We conclude that TRPV1 channels limit the vasomotor responses to changes in pH. While base-induced arterial contraction is regulated primarily by neural TRPV1 channels, acid-induced arterial relaxation is modulated by TRPV1 channels located on nonneural vascular structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium* / drug effects
  • Animals
  • Capsaicin / pharmacology
  • Carotid Arteries / drug effects
  • Carotid Arteries / innervation
  • Carotid Arteries / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Hydrochloric Acid / pharmacology
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Rats, Wistar
  • Skin / blood supply*
  • Sodium Hydroxide / pharmacology
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / drug effects
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Tail
  • Vasoconstriction* / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology
  • Vasomotor System / drug effects
  • Vasomotor System / metabolism*

Substances

  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpv1 protein, rat
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Sodium Hydroxide
  • Hydrochloric Acid
  • Capsaicin