Effect of melatonin on vascular reactivity in pancreatectomized rats (original) (raw)
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Inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 2001
. Melatonin MEL , the principal hormone of the vertebral pineal gland, elicits several neurobiological effects. However, the effects of MEL on vascular tissues are still vague. The first goal of this study was to investigate the effect Ž . of MEL on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline NA Ž . Ž . and phenylephrine PHE and relaxant agents acetylcholine and sodium nitroprusside . In addition, the levels of nitric Ž . Ž . Ž . oxide NO , cGMP, total calcium, lipid peroxides, superoxide dismutase SOD and glutathione GSH were also Ž . investigated in tissue homogenates of rabbit aortic rings preincubated 20 min in MEL with and without contractile agents. Our results revealed that MEL has an endothelium-dependent vaso-relaxant effect and potentiated significantly Ž y4 . the vaso-relaxant effect of acetylcholine. Moreover, MEL 10 M had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with control tissue rings, the levels of lipid peroxides were significantly increased while the levels of GSH, and SOD activities were significantly decreased in tissue homogenates of Ž . aortic rings pre-incubated 20 min in NA or PHE. In addition, the levels of NO and cGMP were significantly lower in tissue rings pre-treated with NA and PHE, respectively. Also, the levels of total calcium were significantly increased only in tissue rings pre-treated with NA. The levels of lipid peroxides were significantly decreased, while the levels of GSH, Ž . NO and cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated 20 min Ž y4 . in MEL 10 M in comparison to ring tissues incubated in NA or PHE alone. In aortic rings incubated in MEL q PHE, the levels of lipid peroxides were significantly lower while the levels of GSH and cGMP and SOD activities were significantly higher than their levels in ring tissues incubated in PHE. In aortic rings incubated in MEL q NA, the levels of lipid peroxides and total calcium were significantly lower while the levels of NO were significantly higher than their levels in ring tissues incubated in NA alone. We conclude that MEL has an endothelium dependent vasorelaxant effect and potentiates the endothelium dependent vasorelaxation induced by acetylcholine. MEL inhibits the contractile responses of aortic rings to NA and PHE. These effects may be, in part, due to re-balancing the pro-oxidantrantioxidants system, lowered calcium content and elevated NO and cGMP levels in vascular tissue. ᮊ .eg A.M. Meki .
Die Pharmazie, 2007
Increased oxidative stress and hemorheological disturbances may play very important roles in the development of microangiopathies in diabetes mellitus. This study was designed to determine the healing effect of melatonin on hemorheological parameters and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Wistar male rats were divided into four groups as control, untreated-diabetic, melatonin-treated control and melatonin-treated diabetic rats. Diabetes was induced by injecting streptozotocin (45 mg/kg, i.p.). Fourteen weeks after inducement of diabetes, melatonin (10 mg/kg) was administered intraperitoneally for 5 days to the rats. Erythrocyte deformability and aggregation were measured by laser differaction analysis (LORCA). Diabetic nephropathy was assessed by histopathologic evaluation and TUNEL stain in the diabetic kidney. Decreased erythrocyte deformability and increased erythrocyte aggregation indices were determined in the diabetic group. Melatonin treatment...
Effect of melatonin on vascular responses in aortic rings of aging rats
2007
In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10 À5 mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 mmol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity.
Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats
European Journal of Pharmacology, 2007
Enhanced oxidative stress and impairments in nitric oxide synthesis and bioavailability are of considerable importance in the pathogenesis of diabetic vascular diseases. The aim of the present work was to evaluate the metabolic effects of pharmacological doses of the melatonin, a known antioxidant, on streptozotocin-induced diabetic damage in rats. We investigated the indolamine's influence on the cellular redox-balance, nitric oxide (NO) level, and the activities of antioxidative defence enzymes, as well as the activities of enzymes involved in phase II detoxication and NADPH-generating pentose phosphate pathway. Blood glucose, glycated hemoglobin, bilirubin, as well as plasma alanine aminotransferase activities increased and body weight was reduced in rats with streptozotocin-induced (60 mg/kg, i.p.) diabetes (25 days). The NO level was markedly increased in diabetic plasma (by 50%) and aortic tissue (by 30%). The hyperglycemia resulted in reduced activities of glutathione peroxidase (by 25%), catalase (by 20%), glucose-6-phosphate dehydrogenase (by 55%) and transketolase (by 40%) in liver tissue of diabetic animals. Melatonin treatment (10 mg/kg, 18 days) did not influence the level of hyperglycemia or glycated hemoglobin and it had little effect on the activities of antioxidative enzymes. However, melatonin markedly reversed the activities of glucose-6-phosphate dehydrogenase and transketolase in liver tissue of diabetic rats. The most pronounced effect of the melatonin administration was the prevention of an increase in nitric oxide levels in blood plasma and aortic tissue during diabetes. In in vitro experiments, nitrosomelatonin formation in the presence of nitrosodonors was observed. This implies that melatonin might operate as an NO scavenger and carrier. Thus, melatonin treatment may have some beneficial effects in controlling diabetic vascular complications.
Diabetes induces changes in melatonin concentrations in peripheral tissues of rat
Neuro endocrinology letters, 2007
Exogenous melatonin was found to protect target organs under conditions of diabetes mellitus, however, concentrations of the hormone in peripheral tissues have not been determined. Therefore the aim of the present study was to measure the daily profile of melatonin levels in the pineal gland, plasma, pancreas, kidney, spleen, duodenum and colon of control and diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg/kg of body weight) and samples were collected over a 24 hr cycle on day 17 after STZ treatment. Melatonin and corticosterone levels were measured directly in plasma and after extraction in the pineal gland and peripheral organs (pancreas, kidney, spleen, duodenum and colon). A significant daily rhythm of melatonin concentrations was found not only in the pineal gland and plasma but also in the pancreas, kidney, spleen and duodenum. The daily pattern of melatonin levels in the colon was arrhythmic without a characteristic night-time increase ...
Effect of melatonin in the rat tail artery: role of K + channels and endothelial factors
British Journal of Pharmacology, 1998
1 The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat. 2 Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and a 1adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation.
Melatonin mediates two distinct responses in vascular smooth muscle
European Journal of Pharmacology, 1998
The pineal hormone melatonin was found to produce two distinct contractile responses in vascular smooth muscle. In isolated rat Ž y10 y7 . caudal artery segments, denuded of endothelium, melatonin 10 -10 M potentiated phenylephrine-induced contractions in a Ž y7 y5 .