ROLE OF NITRIC-OXIDE, ADENOSINE, AND ATP-SENSITIVE POTASSIUM CHANNELSIN INSULIN-INDUCED VASODILATION

The resistance of various tissues to the vasodilator and metabolic eff ects of insulin may be an important risk factor in the genesis of hype rtension observed in several pathological states. Because of this, it is important to understand the mechanisms by which insulin causes vaso dilation. Because insulin is known to raise metabolism, one mechanism by which insulin causes vasodilation could be through metabolic vasodi lation. Recently, however, it has been suggested that the insulin-indu ced vasodilation is mediated by the release of endothelium-derived nit ric oxide. Using a model of muscle microcirculation (hamster cremaster ), we examined the interactions between insulin, nitric oxide, and tis sue 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 m u m (n=8). During nitric oxide synthase inhibition, topical applicatio n of insulin caused significant vasodilation in both second- and fourt h-order arterioles. In contrast, both adenosine receptor antagonism an d blockade of ATP-sensitive potassium channels prevented insulin-induc ed increases in arteriolar diameter. Our findings suggest a role for i ncreased tissue metabolism, particularly the metabolite adenosine, in mediating insulin-induced vasodilation.