CARDIAC VAGAL AFFERENT STIMULATION BY FREE RADICALS DURING ISCHAEMIA AND REPERFUSION
- 1 August 1996
- journal article
- Published by Wiley in Clinical and Experimental Pharmacology and Physiology
- Vol. 23 (8) , 700-708
- https://doi.org/10.1111/j.1440-1681.1996.tb01762.x
Abstract
1. Myocardial ischaemia 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 free radicals, which are well known to be produced during ischaemia and reperfusion, contribute to this excitation. 2. Activity from vagal afferent fibres in rats, whose endings were located in the walls of all four chambers of the heart, was recorded in response to topical application of pro-oxidant chemicals to the surface of the heart. Activity was also recorded from vagal afferent fibres, whose endings were located in the left ventricle, in response to occlusion of the left anterior coronary artery (LAC) for 30 min and subsequent reperfusion. A majority of the recorded fibres were classified as chemosensitive C-fibre endings due to their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1-10 micrograms) to the surface of the heart encompassing the receptive field and their conduction velocities. 3. Topical application of either H2O2 or xanthine/xanthine oxidase to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. This effect was reproducible, dose-dependent and was not due to [H+]. 4. Administration of the superoxide radical scavenging enzyme, superoxide dismutase (20000 U/kg, i.v.), decreased the response of fibres to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidants deferoxamine (20 mg/kg, i.v.) or dimethylthiourea (10 mg/kg, i.v.), which scavenge the hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Administration of indomethacin (5 mg/kg, i.v.) had no effect on the afferent response to H2O2. 5. In response to ligation of the left anterior coronary (LAC), the activity of chemosensitive endings within the ischaemic zone increased within the first 2 min of occlusion. Endings outside the ischaemic zone were not affected at the beginning of ischaemia. Reperfusion activated only chemosensitive endings responsive to topical H2O2. These reperfusion-sensitive endings were located both within and outside the ischaemic zone of the left ventricle. 6. Indomethacin (5 mg/kg, i.v.) prevented activation of chemosensitive endings at the beginning of LAC occlusion regardless of their sensitivity to H2O2 but had no effect on the response to reperfusion. Conversely, deferoxamine (20 mg/kg, i.v.) had no effect on the activation of chemosensitive fibres at the onset of ischaemia, whereas it completely prevented activation at reperfusion. 7. We propose that there are two different mechanisms that activate chemosensitive afferent vagal fibres in the rat heart during ischaemia and reperfusion. The first causes excitation of these endings at the onset of ischaemia and is mediated by prostaglandin synthesis within the ischaemic zone. The second mechanism leads to a more widespread activation of chemosensitive afferents in the left ventricle during prolonged ischaemia and at the moment of reperfusion and is mediated by oxygen free radical formation.Keywords
This publication has 14 references indexed in Scilit:
- Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals.Circulation Research, 1994
- Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.Circulation Research, 1994
- Oxygen-derived free radicals and myocardial reperfusion injury: An overviewCardiovascular Drugs and Therapy, 1991
- Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins.Circulation, 1989
- Coronary reperfusion and Bezold-Jarisch reflex (Bradycardia and Hypotension)The American Journal of Cardiology, 1983
- Cardiovascular reflexes stimulated by reperfusion of ischemic myocardium in acute myocardial infarction.Circulation, 1983
- Cardiovascular Afferents Involved in Regulation of Peripheral VesselsAnnual Review of Physiology, 1980
- Stimulation by bradykinin of afferent vagal C-fibers with chemosensitive endings in the heart and aorta of the dog.Circulation Research, 1980
- The circulatory influences of vagal afferents at rest and during coronary occlusion in conscious dogs.Circulation Research, 1978
- Left Ventricular Receptors Activated by Severe Asphyxia and by Coronary Artery OcclusionActa Physiologica Scandinavica, 1971