Activation of cardiac vagal afferents by oxygen-derived free radicals in rats

Elena E. Ustinova, Harold D. Schultz

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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 μg) 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 μmol (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). Administration of the superoxide radical-scavenging enzyme superoxide dismutase (20 000 U/kg IV) significantly decreased the response of the fibers to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidant deferoxamine (20 mg/kg IV), which prevents the formation of hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Dimethylthiourea (10 mg/kg IV), which scavenges the hydroxyl radical, also abolished afferent responses to H2O2. Administration of indomethacin (5 mg/kg IV) had no effect on the afferent response to H2O2. These results indicate that (1) the rat heart possesses a notable innervation by chemosensitive afferent vagal C fibers, (2) these cardiac chemosensitive afferents can be activated by reactive oxygen species, (3) the hydroxyl radical appears to be more important than the superoxide anion for this activation, and (4) this activation is not mediated by the cyclooxygenase system.

Original languageEnglish (US)
Pages (from-to)895-903
Number of pages9
JournalCirculation Research
Volume74
Issue number5
DOIs
StatePublished - May 1994

Fingerprint

Hydroxyl Radical
Free Radicals
Xanthine
Xanthine Oxidase
Oxygen
Unmyelinated Nerve Fibers
Mechanoreceptors
Superoxides
Reflex
Myocardial Reperfusion
Deferoxamine
Nerve Endings
Capsaicin
Prostaglandin-Endoperoxide Synthases
Cardiovascular System
Indomethacin
Hydrogen Peroxide
Superoxide Dismutase
Reperfusion
Myocardial Ischemia

Keywords

  • antioxidants
  • cardiac chemosensitive endings
  • oxygen radicals
  • prostaglandins
  • ventricular C fibers
  • ventricular receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Activation of cardiac vagal afferents by oxygen-derived free radicals in rats. / Ustinova, Elena E.; Schultz, Harold D.

In: Circulation Research, Vol. 74, No. 5, 05.1994, p. 895-903.

Research output: Contribution to journalArticle

@article{7faaa7f351f9433ea235449228a6958d,
title = "Activation of cardiac vagal afferents by oxygen-derived free radicals in rats",
abstract = "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 μg) 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 μmol (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). Administration of the superoxide radical-scavenging enzyme superoxide dismutase (20 000 U/kg IV) significantly decreased the response of the fibers to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidant deferoxamine (20 mg/kg IV), which prevents the formation of hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Dimethylthiourea (10 mg/kg IV), which scavenges the hydroxyl radical, also abolished afferent responses to H2O2. Administration of indomethacin (5 mg/kg IV) had no effect on the afferent response to H2O2. These results indicate that (1) the rat heart possesses a notable innervation by chemosensitive afferent vagal C fibers, (2) these cardiac chemosensitive afferents can be activated by reactive oxygen species, (3) the hydroxyl radical appears to be more important than the superoxide anion for this activation, and (4) this activation is not mediated by the cyclooxygenase system.",
keywords = "antioxidants, cardiac chemosensitive endings, oxygen radicals, prostaglandins, ventricular C fibers, ventricular receptors",
author = "Ustinova, {Elena E.} and Schultz, {Harold D.}",
year = "1994",
month = "5",
doi = "10.1161/01.RES.74.5.895",
language = "English (US)",
volume = "74",
pages = "895--903",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Activation of cardiac vagal afferents by oxygen-derived free radicals in rats

AU - Ustinova, Elena E.

AU - Schultz, Harold D.

PY - 1994/5

Y1 - 1994/5

N2 - 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 μg) 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 μmol (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). Administration of the superoxide radical-scavenging enzyme superoxide dismutase (20 000 U/kg IV) significantly decreased the response of the fibers to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidant deferoxamine (20 mg/kg IV), which prevents the formation of hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Dimethylthiourea (10 mg/kg IV), which scavenges the hydroxyl radical, also abolished afferent responses to H2O2. Administration of indomethacin (5 mg/kg IV) had no effect on the afferent response to H2O2. These results indicate that (1) the rat heart possesses a notable innervation by chemosensitive afferent vagal C fibers, (2) these cardiac chemosensitive afferents can be activated by reactive oxygen species, (3) the hydroxyl radical appears to be more important than the superoxide anion for this activation, and (4) this activation is not mediated by the cyclooxygenase system.

AB - 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 μg) 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 μmol (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). Administration of the superoxide radical-scavenging enzyme superoxide dismutase (20 000 U/kg IV) significantly decreased the response of the fibers to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidant deferoxamine (20 mg/kg IV), which prevents the formation of hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Dimethylthiourea (10 mg/kg IV), which scavenges the hydroxyl radical, also abolished afferent responses to H2O2. Administration of indomethacin (5 mg/kg IV) had no effect on the afferent response to H2O2. These results indicate that (1) the rat heart possesses a notable innervation by chemosensitive afferent vagal C fibers, (2) these cardiac chemosensitive afferents can be activated by reactive oxygen species, (3) the hydroxyl radical appears to be more important than the superoxide anion for this activation, and (4) this activation is not mediated by the cyclooxygenase system.

KW - antioxidants

KW - cardiac chemosensitive endings

KW - oxygen radicals

KW - prostaglandins

KW - ventricular C fibers

KW - ventricular receptors

UR - http://www.scopus.com/inward/record.url?scp=0028261688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028261688&partnerID=8YFLogxK

U2 - 10.1161/01.RES.74.5.895

DO - 10.1161/01.RES.74.5.895

M3 - Article

C2 - 8156636

AN - SCOPUS:0028261688

VL - 74

SP - 895

EP - 903

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 5

ER -