Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings

Harold D. Schultz, Elena E. Ustinova

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Objective: The effects of capsaicin on sensory neurons are mediated by its interaction with a specific membrane receptor and opening of a non- selective cation channel. In the rat heart, capsaicin-sensitive nerve endings are known to be activated by oxygen radicals. We investigated the possibility that free oxygen radicals stimulate sensory nerve endings by acting upon the capsaicin receptor. Methods: We studied the effects of capsaicin (0.16-16.0 nmol), bradykinin (0.1-10 nmol), H2O2 (1.5-30 μol), and xanthine + xanthine oxidase (X + XO, 1 μmol + 0.03 mU) applied to the surface of the rat heart for 30 s on the activity of cardiac, capsaicin-sensitive, vagal and sympathetic afferent fibers before and after blockade of capsaicin receptors with capsazepine (200 μg/kg, i.v.), a specific antagonist for the capsaicin receptor. Results: Application of capsaicin (0.32-16.0 nmol), H2O2 (9-30 μmol), bradykinin (1-10 nmol), and X + XO increased cardiac vagal and sympathetic afferent activity. Administration of capsazepine had no effect on the baseline activity of either vagal or sympathetic cardiac afferents, but it abolished the response of the afferent fibers to all doses of capsaicin, H2O2, and X + XO tested. Capsazepine had no effect on afferent activation by bradykinin. Administration of another capsaicin receptor blocker, ruthenium red (780 μg/kg, i.v.), had similar effects. Conclusions: The results of these experiments indicate that blockade of capsaicin receptors inhibits activation of vagal and sympathetic cardiac afferent fibers by free oxygen radicals. The fact that capsazepine and ruthenium red did not affect the afferent response to bradykinin suggests that this effect of the blockers was specific for capsaicin receptors. The possible functional implications of this interaction are discussed.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalCardiovascular research
Volume38
Issue number2
DOIs
StatePublished - May 1998

Keywords

  • Capsaicin
  • Capsazepine
  • Cardiac afferent
  • Free radical
  • Rat
  • Ventricular receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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