Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane-receptor-mediated vasoconstriction.
Individuals with hyperglycemia exhibit impaired exercise performance and functional vasodilatory response. Based on the importance of arachidonic acid (AA) metabolites in functional vasodilation and the increased thromboxane-to-prostacyclin ratio in diabetes, we hypothesized that chronic hyperglycemia in diabetes increases thromboxane-receptor (TP)-mediated vasoconstriction, resulting in an attenuated functional vasodilation. Three groups of lean Zucker rats (8 wk) were used to test the effects of chronic hyperglycemia on endothelial function: normal, streptozotocin (STZ; 70 mg/kg ip), and STZ + insulin (2 U/day). After 4 wk of treatment, spinotrapezius arcade arterioles were chosen for microcirculatory observation. Arteriolar diameter was measured following muscle stimulation and 10 microM AA application in the absence and presence of 1 microM SQ-29548 (TP antagonist). STZ rats exhibited significantly higher fasting glucose levels and attenuated functional and AA-induced dilation compared with normal animals. SQ-29548 improved the vasodilatory responses in STZ rats but had no effect in controls. Insulin treatment normalized both the glucose levels and the vasodilatory responses, and SQ-29548 treatment had no effect on functional or AA-mediated vasodilation in STZ + insulin animals. These results suggest that the impaired functional vasodilation in diabetic rats is due to hyperglycemia-mediated increases in TP-mediated vasoconstriction.
Xiang
Lusha
L
Dept. of Physiology and Biophysics, Univ. of Mississippi Medical Center, 2500 North State St., Jackson, MI 39216-4505, USA.
Naik
Jay S
JS
Abram
Sean R
SR
Hester
Robert L
RL
D000818:Animals; D002908:Chronic Disease; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D017482:Receptors, Thromboxane / Q000378:metabolism*; D013311:Streptozocin; D014661:Vasoconstriction; D014664:Vasodilation
D017482:Receptors, Thromboxane; D013311:Streptozocin