Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings.
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 mumol), and xanthine + xanthine oxidase (X + XO, 1 mumol + 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 micrograms/kg, i.v.), a specific antagonist for the capsaicin receptor.


RESULTS
Application of capsaicin (0.32-16.0 nmol), H2O2 (9-30 mumol), 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 micrograms/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.
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198-4575, USA.
H D
HD
Schultz
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EE
Ustinova
D000320:Adrenergic Fibers / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D005609:Free Radicals; D006321:Heart / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012430:Ruthenium Red / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013233:Stellate Ganglion / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D004396:Coloring Agents; D005609:Free Radicals; D017382:Reactive Oxygen Species; D011955:Receptors, Drug; D012430:Ruthenium Red; D019820:Xanthine; D014969:Xanthine Oxidase; C071423:capsazepine; D002211:Capsaicin; D001920:Bradykinin