Vascular reactivity in diabetic rats: effect of melatonin

Abstract

The aim of the present study was to evaluate the in vitro contractile response of rat aorta in mild and severe type I diabetes and the effect of melatonin on it. Aortic rings were obtained from male Wistar rats injected with streptozotocin 8-12 wks earlier. Rats were divided into three groups: non-diabetic rats (NDR), mildly diabetic rats (MDR) and severely diabetic rats (SDR). Dose-response curves for acetylcholine-induced, endothelium-related relaxation of aortic rings (after previous exposure to phenylephrine) and for serotonin-induced vasoconstriction were conducted in the presence or absence of 10-5 mol/L melatonin. This protocol was repeated with rings preincubated in a high glucose solution (44 mmol/L). The contractile response to phenylephrine decreased in SDR, an effect counteracted by preincubation with high glucose. Melatonin decreased phenylephrine-induced vasoconstriction in MDR and counteracted the effect of high glucose in SDR. Acetylcholine-evoked relaxation decreased significantly after exposure to a high glucose in SDR, this effect being counteracted by melatonin. Serotonin-induced vasoconstriction decreased in SDR and augmented in MDR, but only after exposure to high glucose. Melatonin reduced the maximal tension of aortic contraction after serotonin in MDR, both under basal conditions and after preincubation in a high glucose solution. The results support the existence of differences in vasomotor responses as a function of the diabetes state and of an improvement of contractile performance in diabetic rats after exposure to melatonin at a pharmacological concentration (in terms of circulating melatonin levels but not necessarily for some other fluids or tissues).

D-4F Induces Heme Oxygenase-1 and Extracellular Superoxide Dismutase, Decreases Endothelial Cell Sloughing, and Improves Vascular Reactivity in Rat Model of Diabetes

“…35 The present study confirmed a significant impairment in diabetic rats (51Ϯ7% relaxation) compared with controls (77Ϯ3% relaxation). D-4F restored vascular reactivity in diabetic rats to 85Ϯ2% relaxation ( Figure 7A).…”

“…Reactivity of the blood vessels has been shown to be diminished in diabetes. 35 Vascular reactivity in control, untreated diabetic, and D-4F-treated diabetic rats did not differ significantly in the presence of NONOate, which indicates a dependence on the bioavailability of NO. There is an ever-increasing body of evidence that indicates that inflammation and oxidative stress a play major role in the formation of atherosclerotic disease.…”

Vascular Reactivity to Various Vasoconstrictor Agents and Endothelium-Dependent Relaxations of Rat Thoracic Aorta in the Long-Term Period of Pinealectomy

“…Contrary to this idea, our study demonstrated that the endotheliumdependent relaxation response to ACh was similar between Px and control rats. Consistent with our findings, it was reported that melatonin did not affect ACh-induced relaxation in the rat aorta contracted with a submaximal concentration of phenylephrine (25,26). Similarly, Geary et al suggest that melatonin did not affect relaxation responses to either ACh or SNP in endothelium-intact or -denuded rat arteries (27).…”

Multiple Facets of Melatonin in Immunity: Clinical Applications

“…Moreover, melatonin reduces proliferation of splenocytes and Th1 cells, prolonging the survival of pancreatic islet grafts in NOD mice [ 203 ]. Melatonin is not only useful for preventing the development of T1D, but it also shows protective effects against the main complication of the disease, cardiovascular disease, since it improves vascular contractile performance in diabetic rats [ 204 ] and reduces blood pressure in T1D adolescents [ 205 ].…”