Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.
The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity. However, the addition of ONO-2235 (100 microM) prevented the inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition of NO production in HUVEC. this agent might ameliorate endothelial function associated with diabetes.
Okuda
Y
Y
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Japan.
Kawashima
K
K
Suzuki
S
S
Asakura
Y
Y
Asano
M
M
Tsurumaru
K
K
Dai
H
H
Tachi
Y
Y
Bannai
C
C
Saitoh
M
M
Yamashita
K
K
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013012:Sorbitol / Q000378:metabolism; D053778:Thiazolidines; D014471:Umbilical Veins
D003470:Culture Media; D004791:Enzyme Inhibitors; D053778:Thiazolidines; D005632:Fructose; D009569:Nitric Oxide; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase; D005947:Glucose