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Effects of chronic stress and diabetes on antioxidant status and myocardial susceptibility to ischemia/reperfusion injury

University of British Columbia

Diabetes and psychological stress can both be described as states in which the actions of glucocorticoids and catecholamines predominate over those of insulin. Stress has a permissive, albeit poorly defined, effect on the development of myocardial infarction and atherosclerosis, which are major complications of the diabetic state; reactive oxygen radicals have been implicated in both conditions. Therefore, the effects of chronic-intermittent variable restraint stress on antioxidant status and myocardial susceptibility to ischemial/reperfusion injury in control, and streptozotocin diabetic rats were investigated. As an initial approach, the influence of chemical and/or surgical sympathectomy on the, antioxidant status of various tissues was investigated in non-diabetic rats. The effects of acute and chronic stress in diabetic and non-diabetic rats on levels of glucose, corticosterone and catecholamines measured from blood collected through in-dwelling catheters were compared. Antioxidant status of blood and tissues from normal and short- and long-term diabetic rats exposed to stress was assessed in terms of activities of antioxidant enzymes (catalase, superoxide dismutase, g lutathione peroxidase and glutathione reductase), non-enzymatic antioxidants (glutathione, ascorbate and tocopherol) and in vitro peroxide challenge. To determine whether stress-induced alteration in antioxidant capacity in diabetes was a result of the associated hyperlipidemia, non-diabetic rats with diet-induced hyperlipidemia were subjected to stress and resultant effects on plasma lipid profiles and antioxidant components and functional status examined. Finally, the effects of stress on myocardial susceptibility to ischemial/reperfusion injury were investigated in terms of myocardial function and antioxidant status. Studies involving sympathectomy suggested differential actions of adrenaline and noradrenaline on antioxidant components. The corticosterone and catecholamine responses to acute and chronic stress are modified by diabetes. While antioxidant systems are normally resistant to stress, their susceptibility to stress-induced modification increases in diabetes, a pathological condition associated with increased oxidative challenge. Stress-induced changes in plasma lipids and antioxidant components cannot be solely ascribed to the associated hyperlipidemia in diabetes. While some diabetes-associated antioxidant alterations occurred regardless of its duration, other differences related to the long term effects of the disease. The consequences of stress on diabetes-associated antioxidant changes and myocardial susceptibility to ischemial/reperfusion injury were to some extent modified by the duration of diabetes.

Thesis/Dissertation

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2009-04-22

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http://hdl.handle.net/2429/7492

Pharmacology and Therapeutics

University of British Columbia

UBCV

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