Regional hyperinsulinemia induces vasodilation but does not modulate adrenergic responsiveness in humans.

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 alpha- or by augmentation of beta-adrenergic responsiveness. The effect of insulin infusion into the brachial artery (regional forearm hyperinsulinemia; venous insulin concentration approximately 500 pM) on forearm blood flow (FBF: plethysmography) was studied. Responses to the alpha-adrenoceptor-mediated vasoconstrictor norepinephrine (NE: once with and once without the beta-adrenoceptor antagonist propranolol, 2 x n = 12; 9 participated in both), and to the beta-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 beta-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 beta-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 alpha- or beta-adrenergic responsiveness.

journal_name

J Cardiovasc Pharmacol

authors

Tack CJ,Heeremans M,Thien T,Lutterman JA,Smits P

doi

10.1097/00005344-199608000-00010

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

245-51

issue

2

eissn

0160-2446

issn

1533-4023

journal_volume

28

pub_type

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