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1From the Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville Florida; the 2Department of Ophthalmology, College of Medicine, Showa University, Tokyo, Japan; the 3Wake Forest Institute of Regenerative Medicine, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina; and the 4Biomedical Research Models, Inc., Worcester, Massachusetts.
PURPOSE. To evaluate the effect of acute exposure to high glucose on myogenic tone and reactivity of the rat ophthalmic artery and to compare the observations with that in ophthalmic artery from a diabetic rat model.
METHODS. Ophthalmic arteries from Sprague-Dawley rats were pressurized at 70 mm Hg in an arteriograph, and outer diameter was monitored. Myogenic tone was assessed over a range of intraluminal pressures in the presence and absence of high glucose or mannitol. The effects of high glucose on reactivity to carbachol and phenylephrine were determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control rats were evaluated for myogenic tone and reactivity.
RESULTS. Myogenic tone was enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by mannitol. Constriction to phenylephrine was not affected by 25 mM, but was decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected. Effects of high glucose were not observed in the absence of endothelium. Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydro-ouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM glucose. Arteries from diabetic rats showed decreased myogenic tone compared with control arteries, and this decrease was not observed in the absence of endothelium.
CONCLUSIONS. Acute exposure to high glucose has a concentration- and endothelium-dependent effect on the myogenic tone of rat ophthalmic artery. Attenuation of tone by high glucose is probably due to the activation of smooth muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressure-mediated autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at lower resistance, probably due to hyperglycemia.
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