期刊
CIRCULATION RESEARCH
卷 89, 期 2, 页码 146-152出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hh1401.093294
关键词
K+ channels; superoxide; coronary circulation; vascular smooth muscle
资金
- NHLBI NIH HHS [R01 HL-59238, R01 HL-52869] Funding Source: Medline
Hyperglycemia is associated with impaired endothelium-dependent dilation that is due to quenching of NO by superoxide (O(2)radical anion). In small coronary arteries (CAs), dilation depends more on smooth muscle hyperpolarization, such as that mediated by voltage-gated K+ (Kv) channels. We determined whether high glucose. enhances O(2)radical anion production and reduces microvascular Kv channel current and functional responses. CAs from Sprague-Dawley rats were incubated 24 hours in medium containing either normal glucose (NG, 5.5 mmol/L D-glucose), high glucose (HG, 23 mmol/L D-glucose), or L-lucose (LG, 5.5 mmol/L D-glucose and 17 mmol/L L-glucose). O(2)radical anion production was increased in HG arteries. Whole-cell patch clamping showed a reduction of 4-aminopyridine (4-AP)-sensitive current (Kv current) from smooth muscle cells of HG CAs versus NG CAs or versus LG CAs (peak density was 9.95 +/-5.3 pA/pF for HG versus 27.8 +/-6.8 pA/pF for NG and 28.5 +/-5.2 pA/pF for LG; P<0.05). O(2)radical anion generation (xanthine+xanthine oxidase) decreased K+ current density, with no further reduction by 4-AP. Partial restoration was observed with superoxide dismutase and catalase. Constriction to 3 mmol/L 4-AP was reduced in vessels exposed to HG (135%, P<0.05) versus NG (307%) or LG (34 +/-4%). Responses to KCI and nifedipine were, not different among groups. Superoxide dismutase and catalase increased contraction to 4-AP in HG CAs. This is the first direct evidence that exposure of CAs to HG impairs Kv channel activity. We speculate that this O(2)radical anion-induced impairment may reduce vasodilator responsiveness in the coronary circulation of subjects with coronary disease or its risk factors.
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