Insulin modulation of beta-adrenergic vasodilator pathway in human forearm

Background Insulin modulates sympathetic vasoconstriction, but the mechanisms underlying this effect are not completely elucidated. We have recently investigated the insulin effect on the α1- and α2-adrenergic vasoconstriction pathway, where it is still conflicting with the possible insulin influence on the ß-adrenergic vasodilator pathway. The aim of the present study was to investigate this issue. Methods and Results The study was performed on the forearm of healthy humans, and all test substances were infused into the brachial artery at systemically ineffective rates. In five subjects, we evaluated isoproterenol-induced vasodilation (1, 3, 6, and 9 ng·kg-1·min-1) both under control conditions and during insulin infusion (0.05 mU·kg-1·min-1). In another group of five subjects, we tested whether the vasorelaxant effect of sodium nitroprusside (1, 2, 4, and 8 ng·kg-1·min-1) was modified by insulin. Moreover, to explore whether the interaction between insulin and forearm ß-adrenergic pathway participates in insulin modulation of sympathetic-evoked vasoconstriction, we measured in six normal subjects the forearm vascular response to lower-body negative pressure under control conditions and during intrabrachial infusion of insulin alone and in combination with a selective ß-adrenergic blocking agent (propranolol 10 µg/100 mL per minute). Finally, to verify whether insulin interaction with the ß-adrenergic pathway may also account for insulin modulation of α2-adrenergic vasoconstriction, we assessed the vascular response to a selective α2-adrenergic agonist before and after propranolol administration. Insulin exposure potentiated the vascular responsiveness to isoproterenol but did not affect the vasodilator response to sodium nitroprusside. Furthermore, the insulin-induced attenuation of sympathetic vasoconstriction was partially corrected by propranolol. In contrast, the insulin modulation of α2-adrenergic vasoconstriction was not influenced by ß-adrenergic blockade. Conclusions Taken together, our results suggest that insulin modulation of sympathetic-induced vasoconstriction is carried out through an interaction of the hormone with the pathways of both α2- and ß-adrenergic receptors