Effect of chronic and selective endothelin receptor antagonism on microvascular function in Type 2 diabetes

摘要

Several pathways of relaxation have been elucidated in the streptozotocin (STZ) model of Type 1 diabetes, of which nitric oxide (NO) is an important mediator of vascular function (17, 20). In experimental obesity and diabetes, it has been reported that ET-1 and NO interact in regulating vascular tone via the ETA receptors (21, 27). Endothelium-derived hyperpolarizing factor (EDHF) and arachidonic acid pathways have been shown to play an important role in vascular function in insulin-resistant models (16, 22, 23). However, barring these studies, the involvement and cross talk of the ET receptors with the vasodilatory mechanisms in Type 2 diabetes are poorly understood. Thus we tested the hypotheses that ETa receptor blockade would prevent augmented vasoconstriction and improve endothelium-dependent vasorelaxation of mesen-teric resistance arteries and that the antagonism of vasculo-protective ETB receptors would display opposing effects in Type 2 diabetes.