Xue Baojian, Zhao Yuanzi, Johnson Alan Kim, Hay Meredith
Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA.
Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1025-H1032. doi: 10.1152/ajpheart.00021.2008. Epub 2008 Jul 3.
It has been shown that reactive oxygen species (ROS) contribute to the central effect of ANG II on blood pressure (BP). Recent studies have implicated an antihypertensive action of estrogen in ANG II-infused female mice. The present study used in vivo telemetry recording and in vitro living mouse brain slices to test the hypothesis that the central activation of estrogen receptors in male mice inhibits ANG II-induced hypertension via the modulation of the central ROS production. In male wild-type mice, the systemic infusion of ANG II induced a significant increase in BP (Delta30.1 +/- 2.5 mmHg). Either central infusion of Tempol or 17beta-estradiol (E2) attenuated the pressor effect of ANG II (Delta10.9 +/- 2.3 and Delta4.5 +/- 1.4 mmHg), and the protective effect of E2 was prevented by the coadministration of an estrogen receptor, antagonist ICI-182780 (Delta23.6 +/- 3.1 mmHg). Moreover, the ganglionic blockade on day 7 after the start of ANG II infusions resulted in a smaller reduction of BP in central Tempol- and in central E2-treated males, suggesting that estrogen inhibits the central ANG II-induced increases in sympathetic outflow. In subfornical organ slices, the application of ANG II resulted in a 21.5 +/- 2.5% increase in ROS production. The coadministration of irbesartan, an ANG II type 1 receptor antagonist, or the preincubation of brain slices with Tempol blocked ANG II-induced increases in ROS production (-1.8 +/- 1.6% and -1.0 +/- 1.8%). The ROS response to ANG II was also blocked by E2 (-3.2 +/- 2.4%). The results suggest that the central actions of E2 are involved in the protection from ANG II-induced hypertension and that estrogen modulation of the ANG II-induced effects may involve interactions with ROS production.
研究表明，活性氧（ROS）参与了血管紧张素II（ANG II）对血压（BP）的中枢作用。最近的研究表明雌激素对输注ANG II的雌性小鼠具有降压作用。本研究采用体内遥测记录和体外活小鼠脑片，以验证以下假设：雄性小鼠中雌激素受体的中枢激活通过调节中枢ROS生成来抑制ANG II诱导的高血压。在雄性野生型小鼠中，全身输注ANG II可导致血压显著升高（Δ30.1±2.5 mmHg）。中枢输注Tempol或17β-雌二醇（E2）均可减弱ANG II的升压作用（Δ10.9±2.3和Δ4.5±1.4 mmHg），而雌激素受体拮抗剂ICI-182780的共同给药可消除E2的保护作用（Δ23.6±3.1 mmHg）。此外，在ANG II输注开始后第7天进行神经节阻断，在中枢给予Tempol和中枢给予E2治疗的雄性小鼠中，血压降低幅度较小，这表明雌激素可抑制中枢ANG II诱导的交感神经输出增加。在穹窿下器切片中，应用ANG II可导致ROS生成增加21.5±2.5%。血管紧张素II 1型受体拮抗剂厄贝沙坦的共同给药或脑片与Tempol的预孵育可阻断ANG II诱导的ROS生成增加（-1.8±1.6%和-1.0±1.8%）。E2也可阻断对ANG II的ROS反应（-3.2±2.4%）。结果表明，E2的中枢作用参与了对ANG II诱导的高血压的保护，雌激素对ANG II诱导效应的调节可能涉及与ROS生成的相互作用。
