title: Prolonged local forearm hyperinsulinemia induces sustained enhancement of nitric oxide-dependent vasodilation in healthy subjects.
abstract: Systemic hyperinsulinemia induces enhancement of endothelium-dependent vasodilation of healthy subjects. During systemic infusion of insulin, endothelium-dependent vasodilation may be improved through a decrease in the concentration of free fatty acids. To explore the direct effect of continued insulin on the vascular endothelium, the authors infused insulin in the brachial artery for 4 h and measured the effect on endothelium-dependent vasodilation in the human forearm. Thirty-six experiments were performed in healthy subjects, mean age 47.7 +/- 1.1 years. Endothelium-dependent and -independent vasodilatation was studied during intra-arterial infusion of serotonin and sodium nitroprusside (SNP), respectively. Forearm blood flow was measured by plethysmography. Intra-arterial insulin was infused for 240 min at a constant rate and blood flow was measured hourly during stimulation of endothelium-dependent and -independent vasodilation.N(G)-monomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = .016. This increase was maintained for 4 h and was blocked by L-NMMA. The SNP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO.
authors.affiliation: Department of Cardiology Y, Bispebjerg University Hospital, Copenhagen NV, Denmark.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hermann
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Ihlemann
authors.forename: Helena
authors.initials: H
authors.lastname: Dominguez
authors.forename: Christian
authors.initials: C
authors.lastname: Rask-Madsen
authors.forename: Lars
authors.initials: L
authors.lastname: Kober
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
mesh_terms: D000368:Aged; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D007328:Insulin; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D005947:Glucose