Background: Insulin modulates sympathetic vasoconstriction, but the mechanisms underlying this effect are not completely elucidated. We have recently investigated the insulin effect on the alpha 1- and alpha 2-adrenergic vasoconstriction pathway, where it is still conflicting with the possible insulin influence on the beta-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 beta-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 beta-adrenergic blocking agent (propranolol 10 micrograms/100 mL per minute). Finally, to verify whether insulin interaction with the beta-adrenergic pathway may also account for insulin modulation of alpha 2-adrenergic vasoconstriction, we assessed the vascular response to a selective alpha 2-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 alpha 2-adrenergic vasoconstriction was not influenced by beta-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 alpha 2-and beta -adrenergic receptors.