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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Endothelial function has been shown to be defective in hyperlipidaemic patients, and animal studies have suggested that Angiotensin Converting Enzyme (ACE) Inhibitors may prevent arterial damage. In order to see if this also occurs in man, we studied the effect of six months treatment with lisinopril on endothelial function in a group of hypercholesterolaemic patients. METHODS and RESULTS: 40 patients were recruited. Forearm Despite a normal cardiac response to ere was a fall in BP. The failure to increase calf vascular resistance due to the action of insulin on skeletal muscle vasculature may be responsible for postprandial hypotension in the elderly after HC.blood flow via venous occlusion plethysmography was assessed in response to Acetylcholine, and Sodium Nitroprusside. Subjects were then randomised in a double blind fashion to receive either Lisinopril 20mg/day (n=20). or placebo (n=20) for six months. Plethsymography was then repeated. Baseline variables between groups were comparable. Lisinopril group: Blood pressure fell significantly, systolic 145k4 vs. 12854 (P