Serizawa Izumi, Iwasaki Nozomi, Ishida Hirotake, Saito Shin-Ya, Ishikawa Tomohisa
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
Eur J Pharmacol. 2017 Feb 15;797:26-31. doi: 10.1016/j.ejphar.2017.01.013. Epub 2017 Jan 13.
An enhanced vasoconstrictor activity of cutaneous arteries participates in the reduction of skin blood flow induced by cooling stimulation. Raynaud's phenomenon, which is characterized by intense cooling-induced constriction of cutaneous arteries, is more common in women during the period from menarche to menopause. We thus investigated the effect of 17β-estradiol (E2) on cooling-induced reduction of plantar skin blood flow (PSBF) in mouse in vivo. Ovariectomized female ddY mice, anaesthetized with pentobarbital, were treated with tetrodotoxin for eliminating the sympathetic nerve tone and artificially ventilated. The PSBF was measured by laser Doppler flowmetry. Cooling air temperature around the foot from 25 to 20, 15, or 10°C decreased the PSBF in a temperature-dependent manner, which was suppressed by the specific α-adrenoceptor antagonist MK-912. When E2 was intravenously administered as a bolus followed by a constant infusion for 10min just before the cooling stimulation, the cooling-induced reduction of PSBF was facilitated by E2 in a dose-dependent manner. The facilitatory effect of E2 was not induced after the treatment with MK-912. Similar facilitatory effect was induced by an intravenous application of G-1, an agonist of G protein-coupled estrogen receptor (GPER, also termed GPR30). Moreover, the facilitatory effect of E2 was abolished by the GPER antagonist G15. These results suggest that acute administration of E2 leads to the facilitation of cooling-induced, α-adrenoceptor-mediated reduction of skin blood flow via the activation of the non-genomic estrogen receptor GPER.
皮肤动脉增强的血管收缩活性参与了冷却刺激引起的皮肤血流减少。雷诺现象的特征是冷却引起的皮肤动脉强烈收缩，在初潮至绝经期间的女性中更为常见。因此，我们研究了17β-雌二醇（E2）对小鼠体内冷却诱导的足底皮肤血流（PSBF）减少的影响。用戊巴比妥麻醉的去卵巢雌性ddY小鼠，用河豚毒素处理以消除交感神经张力并进行人工通气。通过激光多普勒血流仪测量PSBF。足部周围的冷却空气温度从25℃降至20℃、15℃或10℃，以温度依赖的方式降低了PSBF，这被特异性α-肾上腺素能受体拮抗剂MK-912所抑制。当在冷却刺激前静脉推注E2，然后持续输注10分钟时，E2以剂量依赖的方式促进了冷却诱导的PSBF减少。MK-912处理后未诱导出E2的促进作用。静脉应用G蛋白偶联雌激素受体（GPER，也称为GPR30）的激动剂G-1诱导了类似的促进作用。此外，E2的促进作用被GPER拮抗剂G15消除。这些结果表明，急性给予E2通过激活非基因组雌激素受体GPER导致冷却诱导的、α-肾上腺素能受体介导的皮肤血流减少的促进作用。
