Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species

Baojian Xue, Yuanzi Zhao, Alan Kim Johnson, Meredith Hay

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

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 (Δ30.1 ± 2.5 mmHg). Either central infusion of Tempol or 17β-estradiol (E2) attenuated the pressor effect of ANG II (Δ10.9 ± 2.3 and Δ4.5 ± 1.4 mmHg), and the protective effect of E2 was prevented by the coadministration of an estrogen receptor, antagonist ICI-182780 (Δ23.6 ± 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.

Original languageEnglish (US)
Pages (from-to)H1025-H1032
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • Blood pressure
  • Oxidative stress
  • Sex hormone
  • Subfornical organ

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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