INSULIN MODULATION OF BETA-ADRENERGIC VASODILATOR PATHWAY IN HUMAN FOREARM

Background Insulin modulates sympathetic vasoconstriction, but the mec hanisms 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 wi th the possible insulin influence on the beta-adrenergic vasodilator p athway. The aim of the present study was to investigate this issue. Me thods and Results The study was performed on the forearm of healthy hu mans, and all test substances were infused into the brachial artery at systemically ineffective rates. In five subjects, we evaluated isopro terenol-induced vasodilation (1, 3, 6, and 9 ng . kg(-1). min(-1)) bot h 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 parti cipates in insulin modulation of sympathetic-evoked vasoconstriction, we measured in six normal subjects the forearm vascular response to lo wer-body negative pressure under control conditions and during intrabr achial infusion of insulin alone and in combination with a selective b eta-adrenergic blocking agent (propranolol 10 mu g/100 mL per minute). Finally, to verify whether insulin interaction with the beta-adrenerg ic pathway may also account for insulin modulation of alpha(2)-adrener gic vasoconstriction, we assessed the vascular response to. selective alpha(2)-adrenergic agonist before and after propranolol administratio n. Insulin exposure potentiated the vascular responsiveness to isoprot erenol but did not affect the vasodilator response to sodium nitroprus side. Furthermore, the insulin-induced attenuation of sympathetic vaso constriction was partially corrected by propranolol. In contrast, the insulin modulation of alpha(2)-adrenergic vasoconstriction was not inf luenced by beta-adrenergic blockade. Conclusions Taken together, our r esults suggest that insulin modulation of sympathetic-induced vasocons triction is carried out through an interaction of the hormone with the pathways of both alpha(2)- and beta-adrenergic receptors.