期刊
MICROCIRCULATION
卷 18, 期 6, 页码 487-500出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1549-8719.2011.00109.x
关键词
conducted response; K+ channels; hyperpolarization
资金
- British Heart Foundation
- Wellcome Trust, UK
- British Heart Foundation [FS/08/033/25111] Funding Source: researchfish
Objective: To assess the influence of blocking smooth muscle large conductance Ca2+-activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol. Materials and Methods: Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery. Results: Both ACh- and isoproterenol-stimulated local and conducted dilation with similar magnitudes of decay with distance along the feed artery (2000 mu m: similar to 15% maximum dilation). The gap junction uncoupler carbenoxolone prevented both conducted dilation and intercellular spread of dye through gap junctions. IbTx, TEA or 4-AP, blockers of large conductance Ca2+-activated K+ channels and voltage-gated K+ channels, did not affect conducted dilation to either agonist. A combination of either IbTx or TEA with 4-AP markedly improved the extent of conducted dilation to both agonists (2000 mu m: > 50% maximum dilation). The enhanced conducted dilation was reflected in the hyperpolarization to ACh (2000 mu m: Control, 4 +/- 1 mV, n = 3; TEA with 4-AP, 14 +/- 3mV, n = 4), and was dependent on the endothelium. Conclusions: These data show that activated BKCa and KV-channels serve to reduce the effectiveness of conducted dilation.
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