Impairment of endothelial nitric oxide production by acute glucose overload

Am J Physiol Endocrinol Metab. 2001 Jan;280(1):E171-8. doi: 10.1152/ajpendo.2001.280.1.E171.

Abstract

We examined the effects of acute glucose overload (pretreatment for 3 h with 23 mM D-glucose) on the cellular productivity of nitric oxide (NO) in bovine aortic endothelial cells (BAEC). We had previously reported (Kimura C, Oike M, and Ito Y. Circ Res, 82: 677-685, 1998) that glucose overload impairs Ca(2+) mobilization due to an accumulation of superoxide anions (O(2)(-)) in BAEC. In control cells, ATP induced an increase in NO production, assessed by diaminofluorescein 2 (DAF-2), an NO-sensitive fluorescent dye, mainly due to Ca(2+) entry. In contrast, ATP-induced increase in DAF-2 fluorescence was impaired by glucose overload, which was restored by superoxide dismutase, but not by catalase or deferoxamine. Furthermore, pyrogallol, an O(2)(-) donor, also attenuated ATP-induced increase in DAF-2 fluorescence. In contrast, a nonspecific intracellular Ca(2+) concentration increase induced by the Ca(2+) ionophore A-23187, which depletes the intracellular store sites, elevated DAF-2 fluorescence in both control and high D-glucose-treated cells in Ca(2+)-free solution. These results indicate that glucose overload impairs NO production by the O(2)(-)-mediated attenuation of Ca(2+) entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Aorta, Thoracic / cytology
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Catalase / pharmacology
  • Cattle
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Deferoxamine / pharmacology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology*
  • Fluoresceins
  • Glucose / pharmacology*
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Ionophores / pharmacology
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase / pharmacology
  • Superoxides / metabolism

Substances

  • 4,5-diamino-2-(3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
  • Chelating Agents
  • Fluoresceins
  • Ionophores
  • Superoxides
  • Nitric Oxide
  • Calcimycin
  • Adenosine Triphosphate
  • Catalase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • Glucose
  • Deferoxamine
  • Calcium