Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.
Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P < .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Ustinova
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Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha.
Schultz
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D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000294:innervation*; D006352:Heart Ventricles / Q000294:innervation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D019820:Xanthine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D003676:Deferoxamine; D002211:Capsaicin; D007213:Indomethacin