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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Biphenyl Compounds / pharmacology
  • Blood Pressure / drug effects*
  • Cyclic N-Oxides / pharmacology
  • Data Interpretation, Statistical
  • Estradiol / administration & dosage
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogens / administration & dosage
  • Estrogens / pharmacology*
  • Fulvestrant
  • Hypertension / chemically induced*
  • Hypertension / physiopathology
  • Injections, Intraventricular
  • Irbesartan
  • Male
  • Mice
  • Microscopy, Confocal
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism*
  • Spin Labels
  • Subfornical Organ / physiology
  • Telemetry
  • Tetrazoles / pharmacology


  • Angiotensin II Type 1 Receptor Blockers
  • Biphenyl Compounds
  • Cyclic N-Oxides
  • Estrogens
  • Reactive Oxygen Species
  • Spin Labels
  • Tetrazoles
  • Angiotensin II
  • Fulvestrant
  • Estradiol
  • Irbesartan
  • tempol