title: Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice.
abstract: 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 approximately 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.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine,University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Farzad
authors.initials: F
authors.lastname: Moien-Afshari
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Elmi
authors.forename: Majid
authors.initials: M
authors.lastname: Khazaei
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Rahman
authors.forename: Nada
authors.initials: N
authors.lastname: Sallam
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D005081:Exercise Therapy; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007328:Insulin / Q000097:blood; D051379:Mice; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost