Aldose reductase and myo-inositol in endothelial cell dysfunction caused by elevated glucose.
A possible relationship between aldose reductase activity and myo-inositol levels and endothelium-dependent relaxations was examined in isolated rabbit aorta incubated with elevated concentrations of glucose (44 mM) for 6 hr to mimic hyperglycemic conditions. Rings of aorta incubated in elevated glucose and contracted submaximally by phenylephrine showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with aorta incubated in control (5.5 or 11 mM) glucose. Acetylcholine-induced relaxations of aorta incubated in hyperosmotic mannitol (44 mM) were not different from those incubated in control glucose. Treatment with two structurally unrelated aldose reductase inhibitors, sorbinil or zopolrestat, or supplementation with myo-inositol, prevented the abnormal acetylcholine relaxations of aortic rings caused by elevated glucose. No effects of sorbinil, zopolrestat or myo-inositol were observed on the response to acetylcholine of aorta incubated in control glucose. Neither sorbinil nor myo-inositol affected the increase in release of vasoconstrictor prostanoids caused by elevated glucose. These findings suggest that sorbitol accumulation and myo-inositol depletion contribute to the abnormal endothelial cell function caused by exposure to elevated glucose. The increased release of vasoactive prostanoids is either independent of, or possibly contributes to, the abnormal aldose reductase activity and/or myo-inositol depletion in intact blood vessels exposed to elevated concentrations of glucose.
Tesfamariam
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Robert Dawson Evans Department of Clinical Research, Boston University, School of Medicine, Massachusetts.
Brown
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Cohen
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RA
D000109:Acetylcholine / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D013012:Sorbitol / Q000378:metabolism
D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose; D000109:Acetylcholine