title: Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis.
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 (O2 (∙-)) 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 O2 (∙-) in the OVLT plays an important role in the development of chronic AngII-dependent hypertension.
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Collister
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Taylor-Smith
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Drebes
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nahey
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Zimmerman
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D066278:Organum Vasculosum / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013356:Subfornical Organ / Q000201:enzymology*; D000072105:Superoxide Dismutase-1 / Q000378:metabolism*
chemical_list: D000804:Angiotensin II; D000072105:Superoxide Dismutase-1; D010100:Oxygen