Tep-areenan Patcharin, Kendall David A, Randall Michael D
School of Biomedical Sciences, E-Floor, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Eur J Pharmacol. 2003 Aug 22;476(1-2):139-49. doi: 10.1016/s0014-2999(03)02152-6.
We have investigated the involvement of the endothelium, K+ channels, oestradiol receptors, and Ca2+ influx in 17beta-oestradiol-induced vasorelaxation in rat mesenteric arterial beds and aortae. 17beta-Oestradiol (10 pM-1 mM) caused acute vasorelaxations in mesenteric arterial beds and aortae from male and female rats. In male rat mesenteric vessels and aortae, the vasorelaxations were mostly independent of the endothelium and nitric oxide (NO). However, indomethacin (10 microM) enhanced the relaxant responses to 17beta-oestradiol. In male rat mesenteric beds, 60 mM KCl, tetrabutylammonium chloride (300 microM), 4-aminopyridine (1 mM), and barium chloride (30 microM), charybdotoxin (100 nM), but not glibenclamide (10 microM) and tamoxifen (10 microM), inhibited vasorelaxation to 17beta-oestradiol. In male rat aortae, 60 mM KCl did not affect vasorelaxation to 17beta-oestradiol. However, in the presence of indomethacin, vasorelaxation to 17beta-oestradiol was enhanced but this was sensitive to 60 mM KCl. Pre-treatment with 17beta-oestradiol (100 microM) inhibited CaCl2-induced contraction. The present findings indicate that, in rat mesenteric beds and aortae, 17beta-oestradiol causes acute and potent vasorelaxation which may be enhanced in the presence of a cyclooxygenase inhibitor. In mesenteric arterial bed, 17beta-oestradiol-induced vasorelaxation occurs primarily via activation of K+ channels. In the aorta, vasorelaxations involved activation of K+ efflux when the cyclooxygenase pathway was inhibited, and also inhibition of Ca2+ influx.
我们研究了内皮、钾通道、雌二醇受体和钙离子内流在17β-雌二醇诱导的大鼠肠系膜动脉床和主动脉血管舒张中的作用。17β-雌二醇（10 pM - 1 mM）可引起雄性和雌性大鼠肠系膜动脉床和主动脉的急性血管舒张。在雄性大鼠肠系膜血管和主动脉中，血管舒张大多不依赖于内皮和一氧化氮（NO）。然而，吲哚美辛（10 μM）可增强对17β-雌二醇的舒张反应。在雄性大鼠肠系膜床中，60 mM氯化钾、四丁基氯化铵（300 μM）、4-氨基吡啶（1 mM）、氯化钡（30 μM）、大蝎毒素（100 nM）可抑制对17β-雌二醇的血管舒张，但格列本脲（10 μM）和他莫昔芬（10 μM）则无此作用。在雄性大鼠主动脉中，60 mM氯化钾不影响对17β-雌二醇的血管舒张。然而，在吲哚美辛存在的情况下，对17β-雌二醇的血管舒张增强，但对60 mM氯化钾敏感。用17β-雌二醇（100 μM）预处理可抑制氯化钙诱导的收缩。目前的研究结果表明，在大鼠肠系膜床和主动脉中，17β-雌二醇可引起急性和强效的血管舒张，在环氧化酶抑制剂存在时可能增强。在肠系膜动脉床中，17β-雌二醇诱导的血管舒张主要通过钾通道的激活发生。在主动脉中，当环氧化酶途径被抑制时，血管舒张涉及钾外流的激活，也涉及钙离子内流的抑制。
