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

Summary: The relation betw een insulin resistance/ hyperinsulinemia and cardiovascular disease may be re­ lated to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hy- perinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is acti­ vated, although this does not lead to increase in blood pressure (BP). We hypothesized that insulin could induce vasodilation either by reduction of a- or by augmentation of p-adrenergic responsiveness. The effect of insulin in­ fusion into the brachial artery (regional forearm hyperin­ sulinemia; venous insulin concentration —500 pM) on forearm blood flow (FBF: plethysmography) was studied. Responses to the a-adrenoceptor-mediated vasoconstric­ tor norepinephrine (NE: once with and once without the p- adrenoceptor antagonist propranolol, 2 x n = 12; 9 par­ ticipated in both), and to the p-adrenoceptor-mediated vasodilator isoproterenol (n = 12 ) were measured before and during local hyperinsulinemia. Time/control studies (n = 6) were performed. Insulin alone induced vasodila­ tion, 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 N E (1.25 to 240 ng * d l ' 1 • m l ' 1) induced vasoconstriction that was more pronounced dur­ ing concomitant propranolol infusion (p < 0 .0 0 1 ), indicat­ ing a dose-dependent vasodilatory component in the ef­ fect of NE. Isoproterenol (ISO 0.03 to 10 ng * dl~* ' ini'"1), a pure p-adrenoceptor agonist, induced vasodilation. The percentage changes of FBF-ratio during NE + propran­ olol were similar and not significantly different before and during hyperinsulinemia. The same was true of the re­ sponse to N E alone and the response to ISO. Neither was the intrinsic p-agonist component of N E 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 skel­ etal muscle vascular bed, but this vasodilation is not me­ diated through modulation of a- or p-adrenergic respon­ siven ess. Key Words: Insulin— a-A d ren ocep tor— p- Adrenoceptor— V as odilation.