Aim: Hyperinsulinemia worsens brachial artery endothelial function in healthy subjects, while in vitro and in vivo (in other vascular districts) evidence show that insulin facilitates nitric oxide release and endothelium-dependent dilatation. We evaluated role of sympathetic activation during hyperisulinemia on brachial artery endothelial function.

Methods: In 20 healthy male volunteers (age: 27±5 yrs), endothelium-dependent (flow-mediated dilation, FMD) and -independent (sublingual 25 μg glyceryl trinitrate, GTN) dilation were evaluated by ultrasound and computerized analysis of brachial artery diameter. Measures were taken at −60, −10, 120 and 240 minutes during euglycemic hyperinsulinemic clamp (insulin infusion at 0.25 mU.min−1.kg−1 and 20% glucose at variable rates), in absence (n=10) or presence (n=5) of infusion of clonidine (0.0052 μg.min−1.kg−1).

Results: Insulin infusion raised plasma concentrations from 63±4 to 210±22 pmol/l, without changes in blood pressure or heart rate. Insulin raised plasma noradrenaline (from 260±40 to 333±62 pg/ml, p<0.05). This increase was not observed in the presence of clonidine infusion. No change in FMD was observed during insulin infusion (from 7.2+−0.7 to 7.2±0.5%), while response to GTN was decreased (from 9.1±1.0 to 6.8±0.8%; p<0.05). Infusion of clonidine alone did not modify blood pressure, heart rate, FMD and response to GTN. During insulin clamp in the presence of clonidine infusion, FMD did not change (from 7.4±1.8 to 6.9 ±2.9%, p=n.s.), while response to GTN was increased (from 9.4±1.0 to 12.2±0.8, p<0.05).

Conclusions: In healthy subjects, a modest 4-hour hyperinsulinemia does not alter brachial artery endothelial function, but impairs endothelium-independent response. This effects disappears blocking sympathetic nervous system.