| 14976323 |
Erdos B, Simandle SA, Snipes JA, Miller AW, Busija DW: Potassium channel dysfunction in cerebral arteries of insulin-resistant rats is mediated by reactive oxygen species. Stroke. 2004 Apr;35(4):964-9. Epub 2004 Feb 19.
BACKGROUND AND PURPOSE: Insulin resistance (IR) increases the risk of stroke in humans. One possible underlying factor is cerebrovascular dysfunction resulting from altered K (+) channel function. Thus, the goal of this study was to examine K+ channel-mediated relaxation in IR cerebral arteries. METHODS: Experiments were performed on pressurized isolated middle cerebral arteries (MCAs) from fructose-fed IR and control rats. RESULTS: Dilator responses to iloprost, which are BK (Ca) channel mediated, were reduced in the IR compared with control arteries (19+/-2% versus 33+/-2% at 10 (-6) mol/L). Similarly, relaxation to the K (ATP) opener pinacidil was diminished in the IR MCAs (17+/-2%) compared with controls (38+/-2% at 10 (-5) mol/L). IR also reduced the K (ATP) channel-dependent component in calcitonin gene-related peptide-induced dilation; however, the magnitude of the relaxation remained unchanged in IR because of a nonspecified K+ channel-mediated compensatory mechanism. In contrast, K (ir) channel-mediated relaxation elicited by increases in extracellular [K+] (4 to 12 mmol/L) was similar in the control and IR arteries. Blockade of the K (ir) and K (v) channels with Ba2+ and 4-aminopyridine, respectively, constricted the MCAs in both experimental groups with no significant difference. Pretreatment of arteries with superoxide dismutase (200 U/mL) plus catalase (150 U/mL) restored the dilatory responses to iloprost and pinacidil in the IR arteries. Immunoblots showed that the expressions of the pore-forming subunits of the examined K+ channels are not altered by IR. CONCLUSIONS: IR induces a type-specific K+ channel dysfunction mediated by reactive oxygen species. The alteration of K (ATP) and BK (Ca) channel-dependent vascular responses may be responsible for the increased risk of cerebrovascular events in IR. |
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