Regional Hyperinsulinemia Induces Vasodilation But Does Not Modulate Adrenergic Responsiveness in Humans

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Abstract
The relation between insulin resistance/hyperinsulinemia and cardiovascular disease may be related to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is activated, although this does not lead to increase in blood pressure (BP). We hypothesized that insulin could induce vasodilation either by reduction of α- or by augmentation of β-adrenergic responsiveness. The effect of insulin infusion into the brachial artery (regional forearm hyperinsulinemia; venous insulin concentration ≈500 pM) on forearm blood flow (FBF: plethysmography) was studied. Responses to the α-adrenoceptor-mediated vasoconstrictor norepinephrine (NE: once with and once without the β-adrenoceptor antagonist propranolol, 2 × n = 12; 9 participated in both), and to the β-adrenoceptor-mediated vasodilator isoproterenol (n = 12) were measured before and during local hyperinsulinemia. Time/control studies (n = 6) were performed. Insulin alone induced vasodilation, as indicated by an increase in FBF-ratio (infused/control arm) from 1.2 ± 0.1 to 1.6 ± 0.2, p = 0.009. Increasing dosages of NE (1.25 to 240 ng · dl-1 · ml-1) induced vasoconstriction that was more pronounced during concomitant propranolol infusion (p < 0.001), indicating a dose-dependent vasodilatory component in the effect of NE. Isoproterenol (ISO 0.03 to 10 ng · dl-1 · ml-1), a pure β-adrenoceptor agonist, induced vasodilation. The percentage changes of FBF-ratio during NE + propranolol were similar and not significantly different before and during hyperinsulinemia. The same was true of the response to NE alone and the response to ISO. Neither was the intrinsic β-agonist component of NE influenced by insulin. Repeated NE infusion showed no time- or vehicle effect. We conclude that regional hyperinsulinemia in the physiological range induces local vasodilation in the skeletal muscle vascular bed, but this vasodilation is not mediated through modulation of α- or β-adrenergic responsiveness.