The Effects of Chronic Resveratrol Treatment on Vascular Responsiveness of Streptozotocin-Induced Diabetic Rats

Abstract

Resveratrol (3,4Ј,5-trihydroxystilbene) (RSV) is found in dietary plants, and it is a phytoalexin substantially present in grapes and wines, especially in red wines. Resveratrol has been reported to possess a wide range of pharmacological effects, including anti-inflammatory, anticarcinogenic, antioxidant, estrogenic, antiplatelet, and antimicrobial properties. [1][2][3][4][5][6][7] Resveratrol in red wine has been suggested to be responsible for the "French paradox", decreased risk for coronary artery disease in France.8) The beneficial effects of these compounds seem to be due to their antioxidant/antiradical activities protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. 9)Several reports point to protective acute effects of resveratrol on vascular bed, most indicating its vasodilator effects through direct and/or endothelium dependent mechanisms. [10][11][12] The key regulators of the vasomotor function are vasodilatator nitride oxide (NO) and the vasoconstrictor endothelin-1 (ET-1). Alnaeb et al. demonstrated the number of ET-1 receptors was significantly higher whereas, the expression of endothelial NO synthase (eNOS) was significantly lower when comparing aortas from normal rabbits with these from diabetics ones.13) eNOS expression in aorta was significantly lower in insulin-resistant and diabetes mellitus (DM) rats compared with normal control rats and the decrease was more pronounced in DM rats.14) Resveratrol significantly increased the expression of the gene encoding eNOS, which synthesis the vasodilator molecule NO, and decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1). 15)Resveratrol reduces the generation of H 2 O 2 and normalizes the levels of oxidized glutathione reductase and myeloperoxidase (MPO) activities. By normalization of the reductive oxygen species (ROS) levels, resveratrol limits the oxidative stress, which inhibits NO synthesis by eNOS necessary for vasorelaxation.9) Resveratrol inhibits ET-1 promoter activity, ET-1 mRNA level and strain induced ET-1 secretion. Furthermore, resveratrol inhibits ET-1 surproduction and cytosolic phospholipase A 2 activity stimulated by oxidative stress. 9)Diabetes mellitus is an important health problem and mortality from cardiovascular complications is almost three fold higher in the diabetic population than in the general population.16,17) Oxidative stress is a major factor in the genesis of both macroangiopathy and microangiopathy in diabetes. 18)Unlike single angiogenic factor antagonists, resveratrol has therapeutic value (even at very low concentrations of 1-2.5 mM), as it blocks multiple angiogenic pathways including protein kinase C, vascular endothelial growth factor and cyclooxygenase.9) Resveratrol might have a protective effect on diabetic vascular degeneration with its vasorelaxant, antiangiogenic and hypoglycemic features.The purpose of this study was to investigate the chronic effects of resveratrol on diabetes and vascular response in streptozotocin (STZ) induced ...

Alpha Lipoic Acid Treatment Improved Endothelium-dependent Relaxation in Diabetic Rat Aorta

“…23) The results of this study revealed that the endothelium-dependent relaxant response was reduced in aortas from STZ-induced diabetic rats. Although some researchers asserted that the sensitivity to ACh decreased in diabetes, 24,25) the results of this research, in accordance with those of many previous ones, 21,25,26) revealed that diabetes decreased the responses to ACh in maximum relaxation but not the sensitivity.…”

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

“…Several studies have reported that resveratrol produces a decrease in blood glucose concentration in diabetic rats (44,46,53). In the present study we also found a small, but significant, decrease in blood glucose concentration in rats treated with resveratrol.…”

“…Several investigators have shown that resveratrol has both acute and chronic influences on organ systems (7,8,45,53) and endothelial function of large peripheral blood vessels during T1D (41, 44). The mechanisms that account for the effects of resveratrol on vascular function are varied but appear to involve an increase in the expression of eNOS, an increase in the expression of antioxidant pathways and pathways that might regulate antioxidant responses in cells (including SIRT1 and Nrf2), and/or a decrease in the expression of endothelin (13,22,41,44,47,53,58). Thus resveratrol can limit oxidative stress and restore nitric oxide bioavailability to preserve NOS-dependent reactivity of large peripheral blood vessels.…”

“…Resveratrol has been reported to have a variety of pharmacological effects, including anti-inflammatory, anticarcinogenic, antioxidant, and antiplatelet properties (5,6,20,24,45,55,58). Several investigators have shown that resveratrol has both acute and chronic influences on organ systems (7,8,45,53) and endothelial function of large peripheral blood vessels during T1D (41,44). The mechanisms that account for the effects of resveratrol on vascular function are varied but appear to involve an increase in the expression of eNOS, an increase in the expression of antioxidant pathways and pathways that might regulate antioxidant responses in cells (including SIRT1 and Nrf2), and/or a decrease in the expression of endothelin (13,22,41,44,47,53,58).…”

Resveratrol: A miraculous natural compound for diseases treatment

“…Animal studies clearly confirmed anti‐hyperglycemia effects of RSV and its pancreatic β‐cell protection. The effects of resveratrol in decreasing blood glucose were found in rats with diabetes induced by streptozotocin (STZ) alone and STZ with nicotinamide (NA) (Palsamy & Subramanian, 2010; Silan, 2008). The results of the previous studies have shown that RSV could maintain normoglycemia and protect of pancreatic β‐cells in type 1 diabetics.…”