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Oxygen Sensing: Life and Death of a Cell

Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS

¹Second Department of Internal Medicine, Division of Cardiology, and the ²Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Moriguchi City, Japan

Submitted 10 October 2006 ; accepted in final form 22 January 2007

We investigated the mechanism of exercise-induced late cardioprotection against ischemia-reperfusion (I/R) injury. C57BL/6 mice received treadmill exercise (60 min/day) for 7 days at a work rate of 60–70% maximal oxygen uptake. Exercise transiently increased oxidative stress and activated endothelial isoform of nitric oxide synthase (eNOS) during exercise and increased expression of inducible isoform of NOS (iNOS) in the heart after 7 days of exercise. The mice were subjected to regional ischemia by 30 min of occlusion of the left coronary artery, followed by 2 h of reperfusion. Infarct size was significantly smaller in the exercised mice. Ablation of cardiac sympathetic nerve by topical application of phenol abolished oxidative stress, activation of eNOS, upregulation of iNOS, and cardioprotection mediated by exercise. Treatment with the antioxidant N-(2-mercaptopropionyl)-glycine during exercise also inhibited activation of eNOS, upregulation of iNOS, and cardioprotection. In eNOS^–/– mice, exercise-induced oxidative stress was conserved, but upregulation of iNOS and cardioprotection was lost. Exercise did not confer cardioprotection when the iNOS selective inhibitor 1400W was administered just before coronary artery occlusion or when iNOS^–/– mice were employed. These results suggest that exercise stimulates cardiac sympathetic nerves that provoke redox-sensitive activation of eNOS, leading to upregulation of iNOS, which acts as a mediator of late cardioprotection against I/R injury.

oxidative stress; endothelial nitric oxide synthase; inducible nitric oxide synthase

This article has been cited by other articles:

				D. A. Brown and R. L. Moore Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise J Appl Physiol, November 1, 2007; 103(5): 1894 - 1899. [Abstract] [Full Text] [PDF]