Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis

John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C Zimmerman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O 2 -) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 ± 8 mmHg in AdEmpty rats (n = 6), while rats overexpressing CuZnSOD (n = 8) in the OVLT demonstrated a blood pressure increase of only 18 ± 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction of O 2 -in the OVLT plays an important role in the development of chronic AngII-dependent hypertension.

Original languageEnglish (US)
Article number3959087
JournalOxidative medicine and cellular longevity
Volume2016
DOIs
StatePublished - Jan 1 2016

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Angiotensin II
Superoxide Dismutase
Zinc
Copper
Brain
Hypertension
Subfornical Organ
Rats
Blood pressure
Blood Pressure
Organum Vasculosum
Adenoviridae
Superoxides

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

Cite this

Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis. / Collister, John P.; Taylor-Smith, Heather; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

In: Oxidative medicine and cellular longevity, Vol. 2016, 3959087, 01.01.2016.

Research output: Contribution to journalArticle

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abstract = "Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O 2 -) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 ± 8 mmHg in AdEmpty rats (n = 6), while rats overexpressing CuZnSOD (n = 8) in the OVLT demonstrated a blood pressure increase of only 18 ± 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction of O 2 -in the OVLT plays an important role in the development of chronic AngII-dependent hypertension.",
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