Sofronova Svetlana I, Gaynullina Dina K, Martyanov Andrey A, Tarasova Olga S
Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007 Moscow, Russia; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234 Moscow, Russia.
Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007 Moscow, Russia; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234 Moscow, Russia; Department of Physiology, Russian National Research Medical University, Ostrovitianova street 1, 117997 Moscow, Russia.
Eur J Pharmacol. 2015 Oct 15;765:598-605. doi: 10.1016/j.ejphar.2015.09.037. Epub 2015 Sep 28.
Previously we showed that endothelium of 1-2-weeks old rats exerts an anticontractile effect due to spontaneous NO production which correlates with a higher eNOS expression level compared to adult rats. Oestrogens are powerful regulators of eNOS expression and activity in arterial endothelium. This study tested the hypothesis that anticontractile influence of endothelium in young rats is regulated by endogenous oestrogens. Wistar rats were daily treated with ICI 182,780 or letrozole (oestrogen receptor antagonist and aromatase inhibitor, respectively; s.c., 1mg/kg/day) from the second postnatal day, control pups received vehicle injections. At the age of 10-12-days we studied contraction of saphenous arteries using wire myography. ELISA and qPCR were used to evaluate blood sex steroids levels and mRNA expression in arterial tissue, respectively. Ten-12 days old male rats compared to adult male rats demonstrated 78% higher serum 17β-oestradiol concentration and several-fold increase in mRNA contents of oestrogen receptors (ERα and GPER1). However, treatments with ICI 182,780 or letrozole did not affect arterial sensitivity to methoxamine (α1-adrenoceptor agonist) in 10-12-days old males. The blockade of NO-synthase with L-NNA caused tonic contraction and potentiated the response to methoxamine, these effects were similar in control and both treated groups. The sensitivity of endothelium-denuded saphenous arteries to NO-donor DEA/NO did not differ between control and treated groups as well. In addition, treatments with ICI 182,780 or letrozole did not change eNOS expression level in arterial tissue. Our results suggest that endogenous oestrogens do not regulate anticontractile effect of NO during early postnatal development in rats.
先前我们发现，1至2周龄大鼠的内皮细胞由于自发产生一氧化氮（NO）而发挥抗收缩作用，与成年大鼠相比，这与较高的内皮型一氧化氮合酶（eNOS）表达水平相关。雌激素是动脉内皮中eNOS表达和活性的强大调节剂。本研究检验了以下假设：幼鼠内皮的抗收缩作用受内源性雌激素调节。从出生后第二天开始，对Wistar大鼠每日皮下注射ICI 182,780或来曲唑（分别为雌激素受体拮抗剂和芳香化酶抑制剂，1mg/kg/天），对照幼鼠注射溶媒。在10至12日龄时，我们使用线肌张力测定法研究隐动脉的收缩情况。酶联免疫吸附测定（ELISA）和定量聚合酶链反应（qPCR）分别用于评估血液中性类固醇水平和动脉组织中的mRNA表达。与成年雄性大鼠相比，10至12日龄的雄性大鼠血清17β-雌二醇浓度高78%，雌激素受体（ERα和G蛋白偶联雌激素受体1，GPER1）的mRNA含量增加了几倍。然而，用ICI 182,780或来曲唑处理对10至12日龄雄性大鼠的隐动脉对甲氧明（α1-肾上腺素能受体激动剂）的敏感性没有影响。用L-硝基精氨酸甲酯（L-NNA）阻断一氧化氮合酶会引起强直收缩并增强对甲氧明的反应，这些作用在对照组和两个处理组中相似。对照组和处理组之间，去内皮隐动脉对一氧化氮供体二乙胺/一氧化氮（DEA/NO）的敏感性也没有差异。此外，用ICI 182,780或来曲唑处理不会改变动脉组织中eNOS的表达水平。我们的结果表明，内源性雌激素在大鼠出生后早期发育过程中不调节NO的抗收缩作用。
