Faculty Collaboration Database

Elevated glucose impairs cAMP-mediated dilation by reducing Kv channel activity in rat small coronary smooth muscle cells. Am J Physiol Heart Circ Physiol 2003 Sep;285(3):H1213-9

Date

05/24/2003

Pubmed ID

12763748

DOI

10.1152/ajpheart.00226.2003

Scopus ID

2-s2.0-0041357158 (requires institutional sign-in at Scopus site)   78 Citations

Abstract

Hyperglycemia impairs endothelium-dependent vasodilation. In this study, we examined the effect of high glucose (HG) on vascular smooth muscle function. Rat small coronary arteries were freshly isolated or incubated for 24 h with normal glucose (NG; 5.5 mmol/l) or HG (23 mmol/l). In freshly isolated arteries, dilation to isoproterenol (Iso) was reduced by 3 mmol/l 4-aminopyridine (4-AP; 44 +/- 10% vs. 77 +/- 4%; P < 0.05) and further reduced by 4-AP + iberiotoxin (IbTX; 100 nmol/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 with 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 with 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.

Author List

Li H, Chai Q, Gutterman DD, Liu Y

MESH terms used to index this publication - Major topics in bold

4-Aminopyridine
Adrenergic beta-Agonists
Animals
Blood Glucose
Colforsin
Coronary Vessels
Cyclic AMP
Hyperglycemia
Isoproterenol
Male
Membrane Potentials
Muscle, Smooth, Vascular
Peptides
Potassium Channel Blockers
Potassium Channels
Rats
Rats, Sprague-Dawley
Vasodilation