Previous in vitro studies indicate that insulin modifies vascular reactivity to different agents. We have previously demonstrated that in normotensive humans physiological hyperinsulinemia is associated with an increase of forearm norepinephrine release but does not modify vascular resistance. To explore whether insulin modulates peripheral vasoconstriction induced by reflex sympathetic activation, we studied its effects on forearm hemodynamics (strain-gauge plethysmography) during graded levels of lower body negative pressure (-5, -10, -15, and -20 mm Hg, each for 5 minutes) in normotensive subjects. For this purpose, eight subjects received an intrabrachial artery infusion of regular insulin at a systemically ineffective rate (0.05 milliunits/kg per minute) so that deep-venous insulin levels increased in the experimental forearm from 16.5 +/- 2.9 to 379.6 +/- 30 pmol/L (p < 0.01), whereas arterial insulin levels remained unchanged (from 40.9 +/- 8.6 to 43.1 +/- 7.9 pmol/L, NS). In the control arm, forearm vascular resistance (units) increased from 52.3 +/- 3 to a peak of 78.4 +/- 5 (p < 0.001) during lower body negative pressure. In the insulin-exposed forearm, vascular resistance (46.4 +/- 2 at baseline) remained unchanged during insulin infusion (45.8 +/- 3, NS) and rose to a peak of 54.8 +/- 6 (p < 0.05) during lower body negative pressure. The response of forearm vascular resistance to lower body negative pressure was different in the two forearms (F = 4.506, p < 0.01, repeated-measures analysis of variance with grouping factor). Our results demonstrate that in normotensive subjects local physiological hyperinsulinemia reduces the forearm vasoconstrictive response to reflex sympathetic activation
