EFFECTS OF INSULIN ON VASCULAR-RESPONSES TO MENTAL STRESS AND NOREPINEPHRINE IN HUMAN FOREARM

Essential hypertension is frequently associated with insulin resistance and hyperinsulinemia. In vitro, insulin has vasodilator actions, but its possible hemodynamic effect on muscular vascular beds in humans is a matter of controversy. We investigated the effects of local hyperinsulinemia on the vascular responses to norepinephrine and physiological vasodilation during mental stress in the perfused-forearm model. Nine glucose-tolerant, normotensive, nonobese men (aged 22 to 36 years) participated. Forearm perfusion studies (venous occlusion plethysmography) were performed during random ized, double-blind intrabrachial artery infusions of insulin (to raise plasma insulin 100 mu U/mL) or placebo for 2 hours. A mental stress test and stepwise intra-arterial infusion of norepinephrine (6 to 1200 ng/min) were performed during each infusion. Insulin infusion increased venous plasma insulin to 95.4 mu U/mL and increased net glucose uptake threefold. Insulin had a gradual vasodilator effect (P<.05 by ANOVA), and after 90 minutes blood flow was 36 percent units higher relative to the control arm than during placebo (P=.0005). During mental stress, forearm blood flow increased by 81% (t test, P=.006) and 92% (P=.01) in the study arm during insulin and placebo infusions, respectively (insulin versus placebo, P=NS). An increased forearm blood flow was maintained throughout the mental stress test during insulin infusion (ANOVA, P=.03). Forearm glucose uptake increased during stress, reflecting forearm hyperperfusion since fractional glucose extraction was unaffected by stress. The increased blood flow was maintained throughout the five norepinephrine dose steps (ANOVA, P<.04). The highest norepinephrine dose (1200 ng/min) decreased blood flow by 0.81 (ANOVA, P=.01) and 0.83 (P=.001) mL . min(-1) . 100 mL(-1) from baseline after insulin and placebo, respectively (P=NS). Slopes of individual dose-response curves were similar during the two conditions. Thus, high physiological levels of insulin exert a tonic vasodilator effect with a rightward shift of the dose-response curve to norepinephrine, but insulin does not interfere with the physiological increase in forearm perfusion during mental arousal.