Role of nitric oxide, adenosine, and ATP-sensitive potassium channels in insulin-induced vasodilation

The resistance of various tissues to the vasodilator and metabolic effects of insulin may be an important risk factor in the genesis of hypertension observed in several pathological states. Because of this, it is important to understand the mechanisms by which insulin causes vasodilation. Because insulin is known to raise metabolism, one mechanism by which insulin causes vasodilation could be through metabolic vasodilation. Recently, however, it has been suggested that the insulin-induced vasodilation is mediated by the release of endothelium-derived nitric oxide. Using a model of muscle microcirculation (hamster cremaster), we examined the interactions between insulin, nitric oxide, and tissue metabolism to understand the potential mechanisms by which insulin causes vasodilation. Topical application of insulin (200 mu U/mL) to the cremaster resulted in significant increases in arteriolar diameter. Second-order arteriolar diameter increased from 69.6+/-6 to 79.8+/-5 mu m and fourth-order arteriolar diameter from 11.3+/-1 to 15.1+/-2 mu m (n=8). During nitric oxide synthase inhibition, topical application of insulin caused significant vasodilation in both second- and fourth-order arterioles. In contrast, both adenosine receptor antagonism and blockade of ATP-sensitive potassium channels prevented insulin-induced increases in arteriolar diameter. Our findings suggest a role for increased tissue metabolism, particularly the metabolite adenosine, in mediating insulin-induced vasodilation.