INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION IS NITRIC-OXIDE DEPENDENT - A NOVEL ACTION OF INSULIN TO INCREASE NITRIC-OXIDE RELEASE

The purpose of this study was to examine whether insulin's effect to v asodilate skeletal muscle vasculature is mediated by endothelium-deriv ed nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific i nhibitor of NO synthase, was administered directly into the femoral ar tery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF ) was measured during an infusion of saline (NS) or during a euglycemi c hyperinsulinemic clamp (HIC) designed to approximately double LBF. I n response to the intrafemoral artery infusion of L-NMMA, LBF decrease d from 0.296+/-0.032 to 0.235+/-0.022 liters/min during NS and from 0. 479+/-0.118 to 0.266+/-0.052 liters/min during HIC, P < 0.03. The prop ortion of NO-dependent LBF during NS and HIC was similar to 20% and si milar to 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate wheth er insulin increases EDNO synthesis/release or EDNO action, vasodilati ve responses to graded intrafemoral artery infusions of the endotheliu m-dependent vasodilator methacholine chloride (MCh) or the endothelium -independent vasodilator sodium nitroprusside (SNP) were studied in no rmal subjects during either NS or HIC. LBF increments in response to i ntrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature mo st likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.