Department of Clinical Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
J Pharmacol Sci. 2012;118(3):373-81. doi: 10.1254/jphs.11197fp.
The endothelium in rat mesenteric vascular beds has been demonstrated to regulate vascular tone by releasing mainly endothelium-derived hyperpolarizing factor (EDHF), which is involved in the activation of K(+) channels and gap-junctions. However, it is unclear whether the endothelial system in mouse resistance arteries contributes to regulation of the vascular tone. The present study was designed to investigate the role of the endothelium using acetylcholine and A23187 (Ca(2+) ionophore) in mesenteric vascular beds isolated from male C57BL/6 mice and perfused with Krebs solution to measure perfusion pressure. In preparations with active tone produced by methoxamine in the presence of guanethidine, injections of acetylcholine, A23187, and sodium nitroprusside (SNP) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. The vasodilator responses to acetylcholine and A23187, but not SNP, were abolished by endothelium dysfunction and significantly inhibited by N(ω)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) and tetraethylammonium (K(+)-channel inhibitor) but not glibenclamide (ATP-sensitive K(+)-channel inhibitor). Indomethacin (cyclooxygenase inhibitor) significantly blunted only A23187-induced vasodilation, while 18α-glycyrrhetinic acid (gap-junction inhibitor) attenuated only acetylcholine-induced vasodilation. These results suggest that the endothelium in mouse mesenteric arteries regulates vascular tone by prostanoids, EDHF, and partially by nitric oxide, different from the endothelium of rat mesenteric arteries.
大鼠肠系膜血管床的内皮已被证明通过主要释放内皮衍生超极化因子（EDHF）来调节血管张力，EDHF 参与了 K(+) 通道和缝隙连接的激活。然而，尚不清楚小鼠阻力动脉中的内皮系统是否有助于调节血管张力。本研究旨在使用乙酰胆碱和 A23187（钙离子载体）在雄性 C57BL/6 小鼠肠系膜血管床中研究内皮的作用，并用 Krebs 溶液灌注以测量灌注压。在存在胍乙啶的情况下用甲氧胺产生主动张力的制剂中，乙酰胆碱、A23187 和硝普钠（SNP）的注射导致由于血管舒张而导致灌注压呈浓度依赖性降低。乙酰胆碱和 A23187 的血管舒张反应，但不是 SNP，被内皮功能障碍消除，并且被 N(ω)-硝基-L-精氨酸甲酯（一氧化氮合酶抑制剂）和四乙铵（K(+)通道抑制剂）显著抑制，但不是格列本脲（ATP 敏感性 K(+)通道抑制剂）。吲哚美辛（环加氧酶抑制剂）仅显著削弱 A23187 诱导的血管舒张，而 18α-甘草次酸（缝隙连接抑制剂）仅减弱乙酰胆碱诱导的血管舒张。这些结果表明，与大鼠肠系膜动脉的内皮不同，小鼠肠系膜动脉的内皮通过前列腺素、EDHF 和部分通过一氧化氮来调节血管张力。
