Decreased vascular glucose transporter expression and glucose uptake in DOCA-salt hypertension

Objective Because glucose uptake and metabolism can affect vascular smooth muscle cell function, we proposed that animals with hypertension might deve lop alterations in glucose transporter expression in vascular smooth muscle cells that were responsible for some of the vascular abnormalities charact eristic of hypertension. Design and method Male Sprague-Dawley rats (250-300 g) were left uni-nephre ctomized and either implanted or not with deoxycorticosterone acetate (DOCA , 200 mg/ kg) impregnated silastic. All animals were fed normal rat chow. T he DOCA-implanted rats were given water supplemented to 1% NaCl and 0.2% KC l for 7,14 or 28 days. Results The insulin-response glucose transporter (GLUT4) polypeptide levels were depressed several-fold in aortae and carotid arteries from DOCA-salt hypertensive rats compared with sham rats. Uptake of the glucose analog, 2- deoxyglucose (2-DOG), was also reduced 53% in hypertensive compared with sh am aortae. There were no changes in GLUT4 expression in other tissues in th e DOCA-salt animals, nor were there significant changes in aortae from spon taneously hypertensive rat/stroke prone animals. As previously demonstrated , carotid arteries from DOCA-salt animals exhibited a significant increased contractile sensitivity to ergonovine. Inhibition of glucose metabolism wi th 2-DOG in sham arteries caused a marked enhancement of contractile respon siveness to ergonovine, whereas 2-DOG had no effect on the already enhanced contractility of DOCA-salt arteries, suggesting that reduction in glucose uptake and metabolism substantially increases the contractile response of D OCA-salt arteries. Conclusions Alterations in glucose uptake and metabolism in vascular smooth muscle cells may participate in the contractile abnormalities characterist ic of certain forms of hypertension. (C) 2001 Lippincott Williams & Wilkins .