Sandow Shaun L, Goto Kenichi, Rummery Nicole M, Hill Caryl E
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
J Physiol. 2004 May 1;556(Pt 3):875-86. doi: 10.1113/jphysiol.2003.058669. Epub 2004 Feb 6.
A role for myoendothelial gap junctions (MEGJs) has been proposed in the action of the vasodilator endothelium-derived hyperpolarizing factor (EDHF). EDHF activity varies in disease and during ageing, but little is known of the role of EDHF during development when, in many organ systems, gap junctions are up-regulated. The aims of the present study were therefore to determine whether an up-regulation of heterocellular gap junctional coupling occurs during arterial development and whether this change is reflected functionally through an increased action of EDHF. Results demonstrated that in the saphenous artery of juvenile WKY rats, MEGJs were abundant and application of acetylcholine (ACh) evoked EDHF-mediated hyperpolarization and relaxation in the presence of N(omega)-nitro-l-arginine methyl ester (L-NAME) and indomethacin to inhibit nitric oxide and prostaglandins, respectively. Responses were blocked by a combination of charybdotoxin plus apamin, or 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) plus apamin, or by blockade of gap junctions with the connexin (Cx)-mimetic peptides, (43)Gap26, (40)Gap27 and (37,43)Gap27. On the other hand, we found no evidence for the involvement of the putative chemical mediators of EDHF, eicosanoids, L-NAME-insensitive nitric oxide, hydrogen peroxide or potassium ions, since 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE), hydroxocobalamin, catalase or barium and ouabain were without effect. In contrast, in the adult saphenous artery, MEGJs were rare, EDHF-mediated relaxation was absent and hyperpolarizations were small and unstable. The present study demonstrates that MEGJs and EDHF are up-regulated during arterial development. Furthermore, the data show for the first time that this developmentally regulated EDHF is dependent on direct electrotonic coupling via MEGJs.
肌内皮间隙连接（MEGJs）在血管舒张因子内皮源性超极化因子（EDHF）的作用中被认为发挥了一定作用。EDHF的活性在疾病状态和衰老过程中会发生变化，但在发育过程中，当许多器官系统中的间隙连接上调时，EDHF的作用却鲜为人知。因此，本研究的目的是确定在动脉发育过程中异细胞间隙连接耦合是否上调，以及这种变化是否通过EDHF作用增强在功能上得到体现。结果表明，在幼年WKY大鼠的隐动脉中，MEGJs丰富，在分别存在N（ω）-硝基-L-精氨酸甲酯（L-NAME）和吲哚美辛以抑制一氧化氮和前列腺素的情况下，应用乙酰胆碱（ACh）可诱发EDHF介导的超极化和舒张。用查卡毒素加阿帕明、或1-[(2-氯苯基)二苯基甲基]-1H-吡唑（TRAM-34）加阿帕明，或用连接蛋白（Cx）模拟肽（43）Gap26、（40）Gap27和（37,43）Gap27阻断间隙连接，可阻断这些反应。另一方面，我们没有发现EDHF的假定化学介质（类花生酸、L-NAME不敏感的一氧化氮、过氧化氢或钾离子）参与的证据，因为14,15-环氧二十碳-5（Z）-烯酸（14,15-EEZE）、羟钴胺素、过氧化氢酶或钡和哇巴因均无作用。相反，在成年隐动脉中，MEGJs很少见，EDHF介导的舒张不存在，超极化小且不稳定。本研究表明，MEGJs和EDHF在动脉发育过程中上调。此外，数据首次表明，这种发育调控的EDHF依赖于通过MEGJs的直接电紧张耦合。
