Effects of sympathectomy and nitric oxide synthase inhibition on vascular actions of insulin in humans

Insulin exerts cardiovascular actions by stimulating nitric oxide (NO) rele ase and sympathetic neural outflow. It is unclear, however, whether insulin stimulates muscle blood flow (and NO release) by a direct action at the va sculature and/or by stimulating neural vasodilator mechanisms. In these stu dies we used patients with regional sympathectomy to examine the vascular a ctions of insulin in the presence and absence of sympathetic vasoconstricto r and vasodilator innervation. A 2-hour insulin (6 pmol/kg per minute)/gluc ose clamp increased muscle blood flow in both innervated and denervated lim bs by roughly 40% (P<0.01 versus baseline for both limbs). The vasodilation reached its maximum within the first 30 to 35 minutes of insulin/glucose i nfusion in sympathetically denervated limbs, but only at the end of the inf usion in innervated limbs (P<0.01, denervated versus innervated limb). Infu sion of a NO synthase inhibitor (NG-monomethyl-L-arginine [L-NMMA]) increas ed baseline arterial pressure, abolished the vasodilation in the denervated limb, and led to a significant additional increase in arterial pressure du ring the clamp, but did not alter whole body glucose uptake. Our data indic ate that insulin stimulates blood flow in sympathectomized limbs by a direc t action at the vasculature. This effect is mediated by stimulation of NO r elease and appears to be masked by the sympathetic vasoconstrictor tone in innervated limbs.