Effect of glucose on Na, K-ATPase activity in cultured bovine aortic endothelial cells.
The effect of high concentrations of glucose on Na, K-ATPase activity and the polyol pathway was studied using cultured bovine aortic endothelial cells. Na, K-ATPase activity was expressed as ouabain-sensitive K+ uptake. A significant decrease in Na, K-ATPase activity with an intracellular accumulation of sorbitol was found in confluent endothelial cells incubated with 400 mg/dl glucose for 96 h. However, there was no significant change in the Na, K-ATPase activity or sorbitol content of the cells incubated with 100 mg/dl glucose plus 300 mg/dl mannitol. The decrease in Na, K-ATPase induced by the high glucose concentration was restored by the simultaneous addition of 10(-4) M ponalrestat (ICI 128,436; Statil), an aldose reductase inhibitor. The addition of this agent also significantly reduced the increase in sorbitol induced by high glucose levels. These results suggest that the decrease in Na, K-ATPase activity induced in cultured aortic endothelial cells by high concentrations of glucose may be caused in part by the accumulation of sorbitol.
Yamashita
T
T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Umeda
F
F
Hashimoto
T
T
Inoguchi
T
T
Yamauchi
T
T
Mimura
K
K
Watanabe
J
J
Nawata
H
H
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D002417:Cattle; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000209:etiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005947:Glucose / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D010793:Phthalazines; C042829:ponalrestat; D010042:Ouabain; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D011188:Potassium