ABSTRACT
Increased oxidative stress is one of the basic contributors to the development of the cardiovascular complications in diabetes. Both endothelial and vascular smooth muscle cell dysfunctions are the main sign involved in the pathogenesis of diabetic cardiovascular dysfunction. Matrix metalloproteinases (MMPs) are expressed in the vasculature, and participate in tissue remodeling under pathological conditions such as increased oxidative stress, whereas little is known about effect of hyperglycemia on regulation of MMPs in vascular system. Therefore, we aimed to evaluate the effect of an antioxidant, sodium selenate treatment (0.3 mg/kg for 4 weeks) on function of streptozotocin-diabetic rat aorta. Sodium selenate treatment improved significantly impaired isoproterenol-induced relaxation responses and contraction responses of the aortic strips, and exhibited marked protection against diabetes-induced degenerative changes in the smooth muscle cell morphology. Biochemical data showed that sodium selenate treatment induced a significant regulation of MMP-2 activity and protein loss as well as normalization of increased levels of tissue nitrite and protein thiol oxidation. In addition, this treatment restored diabetes-induced increased levels of endothelin-1, PKC, and cAMP production in the aortic tissue. Taken together, our data demonstrate that these beneficial effects of sodium selenate treatment in diabetics are related to be not only inhibition of increased oxidative stress but also prevention of both receptor- and smooth muscle-mediated dysfunction of vasculature, in part, via regulation of MMP-2. Such an observation provides evidence for potential therapeutic usage of selenium compounds for the amelioration of vascular disorders in diabetes.
Subject(s)
Antioxidants/pharmacology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Diabetes Mellitus, Experimental/metabolism , Receptors, Adrenergic, beta/metabolism , Selenium Compounds/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Antioxidants/therapeutic use , Aorta, Thoracic/cytology , Blood Glucose/metabolism , Cyclic AMP/metabolism , Diabetes Mellitus, Experimental/drug therapy , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Isoproterenol/pharmacology , Male , Matrix Metalloproteinases/metabolism , Nitrites/metabolism , Oxidative Stress , Rats , Rats, Wistar , Selenic Acid , Selenium Compounds/therapeutic use , Sulfhydryl Compounds/metabolism , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasodilation/drug effects , Vasodilation/physiologyABSTRACT
The present study was designed to determine whether there are beneficial effects of intake of Omega-3E (containing 70% pure omega-3 and 2% natural vitamin E) in cardiac dysfunction of diabetic rats. We also examined whether there are gender-related differences in the responses to the intake of Omega-3E on the heart dysfunction. Experiments were performed by using Langendorff-perfused hearts from normal, diabetic (with 50 mg/kg streptozotocin), and Omega-3E (50 mg/kg body weight/day) treated diabetic 3-month-old Wistar rats. Omega-3E treatment of the diabetics caused small, but significant decrease (13% and 14% female versus male) in the blood glucose level. Omega-3E treatment of the diabetic female rats did not prevent diabetes-induced decrease in left ventricular developed pressure (LVDP) and increase in left ventricular end-diastolic pressure (LVEDP) with respect to the control female rats. On the other hand, the treatment of diabetic male rats caused significant recovery in depressed LVDP. Furthermore, such treatment of diabetic female and male rats caused significant recovery in depressed rates of changes of developed pressure. This effect was more significant in males. Besides, Omega-3E caused significant further lengthening in the diabetes-induced increased time to the peak of the developed pressure in females, while it normalized the lengthening in the relaxation of the developed pressure in diabetic males. In addition, Omega-3E treatment caused significant restorations in the diabetes-induced altered activities of antioxidant enzymes without any significant gender discrepancy. Present data show that there are gender related differences in diabetic heart dysfunction and the response to antioxidant treatment.
