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Increase in insulin-induced relaxation of consecutive arterial segments toward the periphery: Role of vascular oxidative state

Abstract Rationale. The oxidative state has been implicated in the signaling of various vasomotor functions, yet its role regarding the vasomotor action of insulin is less known. Objective. To investigate the insulin-evoked relaxations of consecutive arterial segments of different oxidative state and the role of extracellular signal-regulated kinase (ERK) pathway. Methods and Results. The oxidative state, as assessed by the level of ortho-tyrosine, was higher in the thoracic aorta of rats than in the abdominal aorta, and was the lowest in the femoral artery. The vasomotor function of vessels of same origin was studied using a small-vessel myograph. Insulin-induced relaxations increased toward the periphery (i.e., thoracic < abdominal < femoral). Aortic banding and hydrogen peroxide/aminotriazole increased the oxidative state of the thoracic aorta that was accompanied by ERK activation and decreased relaxation to insulin, and vice versa, acutely lowered oxidative state by superoxide dismutase/catalase improved relaxation. In contrast, insulin-induced relaxation of the femoral artery could be enhanced with a higher oxidative state, and reduced with a lower state. Conclusions. Oxidative state of vessels modulates the magnitude of vasomotor responses to insulin, which appears to be mediated via the ERK signaling pathway.