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Objective: There is evidence that insulin produces vasodilatation by promoting endothelial nitric oxide release. We investigated the effect of a local insulin infusion on forearm blood flow with coinfusion of either L-NMMA (the substrate inhibitor of nitric oxide synthase), angiotensin I1 (ANG 11) or placebo.Design and Methods: Ten healthy male volunteers were studied on three occasions in a double-blind, random-order, placebocontrolled design. Changes in forearm blood flow ratio were assessed at ten-minute intervals using bilateral venous-occlusion strain-gauge plethysmography. After baseline readings, D-glucose (75ymol/min) was infused for 30 minutes via the brachial artery along with either L-NMMA (4pmol/min), ANG I1 (2Opmol/min) or placebo. Insulin (5mU/min) was then co-infused for a further 90 minutes. Blood was sampled from a deep forearm vein for estimation of insulin, glucose and potassium concentrations. The Wilcoxon Signed Rank Test was used for statistical analysis.Results: Significant forearm vasoconstriction occurred with L-[median (interquartile range)]. Insulin and D-glucose infusion caused significant vasodilatation on the placebo day [30.9% (5.7, 49.4)] (p<0.05). However, insulin had no significant effect on either L-NMMA induced vasoconstriction [-32.6% (-49.4,-18.5)1 or ANG I1 induced vasoconstriction [-26.2% (-35.2,-9.2)l. Local infusion of insulin and D-glucose causes significant forearm vasodilatation. Co-infusion of either L-NMMA or ANG I1 abolishes this effect. We conclude that insulin may exert its vascular effects by promoting endothelial nitric oxide release, but other mechanisms may also be involved.NMMA [-40.6% (-50.8,-19.l)]a11d ANG I1 [-27.9% (-41.7,-20.8 )],Conclusions:

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