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 develop alterations in glucose transporter expression in vascular smooth muscle cells that were responsible for some of the vascular abnormalities characteristic of hypertension.


METHODS
Male Sprague-Dawley rats (250-300 g) were left uni-nephrectomized and either implanted or not with deoxycorticosterone acetate (DOCA, 200 mg/kg) impregnated silastic. All animals were fed normal rat chow. The DOCA-implanted rats were given water supplemented to 1% NaCl and 0.2% KCl 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 sham aortae. There were no changes in GLUT4 expression in other tissues in the DOCA-salt animals, nor were there significant changes in aortae from spontaneously 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 with 2-DOG in sham arteries caused a marked enhancement of contractile responsiveness 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 DOCA-salt arteries.


CONCLUSIONS
Alterations in glucose uptake and metabolism in vascular smooth muscle cells may participate in the contractile abnormalities characteristic of certain forms of hypertension.
Atkins
K B
KB
Department of Internal Medicine, University of Michigan Medical School, East Lansing, Michigan 48109-0676, USA.
Johns
D
D
Watts
S
S
Clinton Webb
R
R
Brosius
F C
FC
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002339:Carotid Arteries / Q000503:physiopathology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003900:Desoxycorticosterone; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006019:Glycolysis; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D010455:Peptides / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D020521:Stroke / Q000235:genetics; D014018:Tissue Distribution; D014661:Vasoconstriction
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010455:Peptides; C495694:Slc2a4 protein, rat; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003847:Deoxyglucose; D005947:Glucose