Diabetes represents a serious risk factor for the development of cardiovascular problems such as coronary heart disease, peripheral arterial disease, hypertension, stroke, cardiomyopathy, nephropathy and retinopathy. Identifying the pathogenesis of this increased risk provides a basis for secondary intervention to reduce morbidity and mortality in diabetic patients. Hyperglycemia and protein glycation, increased inflammation, a prothrombotic state and endothelial dysfunction have all been implicated as possible mechanisms for such complications. A linking element between many of these phenomena could possibly be, among other factors, increased production of reactive oxygen species. Vascular endothelial cells have several physiological actions that are essential for the normal function of the cardiovascular system. These include the production of nitric oxide (NO), which regulates vasodilatation, anticoagulation, leukocyte adhesion, smooth muscle proliferation and the antioxidative capacity of endothelial cells. However, under conditions of hyperglycemia, excessive amounts of superoxide radicals are produced inside vascular cells and this can interfere with NO production leading to the possible complications. This article aims at reviewing the links between reactive oxygen species, diabetes and vascular disease and whether or not antioxidants can alter the course of vascular complications in diabetic patients and animal models. A possible beneficial effect of antioxidants might present a new addition to the range of secondary preventive measures used in diabetic patients.

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Aim: To investigate the possible role of oxidative stress as a common mediator of apoptosis and cardiac damage in diabetes. Materials and Methods:This experimental work was conducted on 5 groups of Wistar rats. Group I was the control group. Diabetes type 1 was induced in other groups (by streptozotocin) and animals received insulin or vitamin E (300 mg /kg body weight), both insulin and vitamin E, or no treatment for 4 weeks according to their group. At the end of the study, serum and cardiac tissues were examined for biochemical parameters of cardiac function, oxidative stress and apoptosis. Electron microscopy pictures of cardiac tissue were also evaluated for signs of cardiac damage.Results: Markers of oxidative stress, apoptosis, inflammation as well as manifestations of cardiac damage as assessed by electron microscopy were significantly decreased in rats treated with both insulin and vitamin E when compared with untreated diabetic rats or rats treated with either insulin or vitamin E alone.Conclusion: Administration of both vitamin E and insulin was effective in reducing markers of oxidative stress and apoptosis and improving parameters of cardiac function in experiments animals. Antioxidants might prove beneficial as an adjuvant treatment in addition to insulin in type 1 diabetes associated with manifestations of cardiac complications.

Numerous studies have shown that increased oxidative stress (OxS) is present in diabetic patients. There is evidence that this OxS can be increased before complications associated with diabetes mellitus (DM) occur. However, the role and influence of OxS in the initiation and progression of DM remains the subject of debate. It has been suggested that in DM, OxS is caused by increased production of reactive oxygen species (ROS), and associated with reduction in antioxidant defenses and altered cellular redox status. Acute and chronic OxS which could enhance the development of complications associated with DM. This review considers recent findings on the role of antioxidants in controlling OxS and the incidence of DM with emphasis on animal and human studies.

The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field.

The role of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in mediating hypoxic preconditioning under the acute intermittent hypoxic condition (AIH) was investigated in this study. Male Wistar rats were randomly assigned and kept in normoxic conditions, (Nx) or in AIH conditions and subjected to brief cycles hypoxia/reoxygenation. Hearts were isolated, perfused, and subjected to in vitro global ischemia followed by reperfusion. During and at the end of reperfusion, left ventricular developed pressure (LVDP); LV end diastolic pressure (LVEDP); rate pressure product (RPP); peak left ventricular pressure rise (DeltaP/Deltat (max) ) and heart rate (HR) were measured. Hearts subjected to AIH displayed a significant higher LVDP (P < .001), RPP (P < .001), and DeltaP/Deltat ( max) (P < .001). Expression of VEGF and EPO were significantly increased at 3, 8, and 24 hours after AIH. Hypoxic training could provide a new approach to enhance endogenous cardioprotective mechanisms.

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.

Cardiovascular disease (CVD) is among the most major causes of morbidity and mortality worldwide. Great progress has been made in the management of CVD which has been influenced by the use of experimental animal models. These models provided information at cellular and molecular levels and allowed the development of treatment strategies. CVD models have been developed in many species, including large animals (e.g. pigs and dogs) and small animals (e.g. rats and mice). Although, no model can solely reproduce clinical HF, simulations of heart failure (HF) are available to experimentally tackle certain queries not easily resolved in humans. Induced HF may also be produced experimentally through myocardial infarction (MI), pressure loading, or volume loading. Volume loading is useful to look at hormone and electrolyte disturbances, while pressure loading models is helpful to study ventricular hypertrophy, cellular imbalance and vascular changes in HF. Coronary heart disease is assessed in MI animal models. In this review we describe various experimental models used to study the pathophysiology of HF.