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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/H1470    most recent 00016.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Moien-Afshari, F. Articles by Laher, I. PubMed PubMed Citation Articles by Moien-Afshari, F. Articles by Laher, I.

Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice

¹Department of Pharmacology and Therapeutics, Faculty of Medicine, and ³Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and ²Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran

Submitted 7 January 2008 ; accepted in final form 2 July 2008

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

coronary artery; manganese superoxide dismutase; diabetes; endothelium; oxidative stress