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1 Departments of Internal Medicine and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
2 Departments of Internal Medicine and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Zablocki VA Medical Center, Milwaukee, Wisconsin, USA
* To whom correspondence should be addressed. E-mail: ypliu{at}mcw.edu.
Hyperglycemia impairs endothelial dependent vasodilation. In this study we examined the effect of high glucose (HG) on vascular smooth muscle function. Rat small coronary arteries (RSCA) were freshly isolated or incubated (24-hour) with normal glucose (NG, 5.5mmol/L) or HG (23mmol/L). In freshly isolated arteries, dilation to isoproterenol (ISO) was reduced by 3mmol/L 4-aminopyridine (4-AP; 44±10% vs 77±4%; p<0.05) and further reduced by 4-AP+iberiotoxin (IBTX, 100nmol/L; 17±2%). Dilation to forskolin was abolished by 4-AP (-3±17 vs 73±9%). cAMP production was similar in NG and HG vessels. Dilations to ISO and forskolin were significantly reduced in HG arteries (ISO: 41±5% vs 70±6%, forskolin: 40±4% vs 75±4%) compared to NG arteries. A similar reduction was also observed to the dilation to papaverine. Endothelial denudation had no effect on ISO-induced dilation. In HG vessels the reduced 4-AP-sensitive component of ISO-induced dilation was greater compared to the IBTX-sensitive component. ISO increased whole-cell K+ current in NG cells, but had little effect in HG cells. Similarly, 4-AP-but not IBTX-sensitive K+ currents were reduced in HG cells. These results suggest that HG impairs cAMP-mediated dilation primarily by reducing Kv channel function. We speculate that in addition to the endothelial dysfunction, altered smooth muscle function may also contribute to the reduced coronary vasodilation in diabetes.
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