title: Local 24-h hyperglycemia does not affect endothelium-dependent or -independent vasoreactivity in humans.
abstract: Hyperglycemia induces regional hemodynamic changes, as suggested by animal studies. These hemodynamic changes may play an initiating role in the pathogenesis of diabetic microangiopathy. The aim of the present study was to evaluate the effects of acute local hyperglycemia for 24 h on basal human forearm muscle and skin blood flow and endothelium-dependent and -independent vasoreactivity. Local hyperglycemia (approximately 15 mM) was induced by infusion of 5% glucose into the brachial artery of the nondominant arm. In control experiments, the same individual amount of glucose was infused intravenously in the dominant arm to correct for possible systemic effects of the infused glucose. Vasoreactivity of the forearm vasculature was evaluated by local infusion of acetylcholine (ACh), sodium nitroprusside (SNP), NG-monomethyl-L-arginine (L-NMMA), and norepinephrine (NE) into the brachial artery. Regional hemodynamic measurements were performed at baseline and after 6, 12, and 24 h of local hyperglycemia. Median (with interquartile range) basal forearm (muscle) blood flow (FBF) was not influenced by the 24-h local hyperglycemia [infused-to-contralateral arm FBF ratio for glucose 1.32 (1.16-1.64) vs. control 1.54 (1.34-1.69)]. Skin microcirculatory blood flow (laser Doppler flowmetry, LDF) was not influenced by the 24-h local hyperglycemia [LDF ratio for glucose 1.00 (0.62-1.56) vs control 0.80 (0.58-1.14)]. In addition, the vasoreactivity of both muscle and skin (not shown) vasculature to ACh [percent change in FBF ratio for glucose 167% (81-263) vs. control 148% (94-211)], SNP [for glucose 486% (178-586) vs. control 293% (196-454)], L-NMMA [for glucose -36% (-56 to -22) vs. control -41% (-51 to -24)], and NE [for glucose -48% (-72 to -41) vs. control -66% (-79 to -33)] was also not affected by the local hyperglycemia. Thus, in contrast to animal studies, our results suggest that a moderate-to-severe hyperglycemia does not affect the regulation of basal blood flow or endothelium-dependent or -independent vasoreactivity in humans.
authors.affiliation: Department of Internal Medicine, University Hospital Maastricht, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Houben
authors.forename: N C
authors.initials: NC
authors.lastname: Schaper
authors.forename: C H
authors.initials: CH
authors.lastname: de Haan
authors.forename: F C
authors.initials: FC
authors.lastname: Huvers
authors.forename: D W
authors.initials: DW
authors.lastname: Slaaf
authors.forename: P W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: C
authors.initials: C
authors.lastname: Nieuwenhuijzen Kruseman
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D006728:Hormones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine