title: Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.
abstract: The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·- in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·- in the MnPO contributes to 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. colli066@umn.edu.
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. bellr007@umn.edu.
authors.forename: Mitch
authors.initials: M
authors.lastname: Bellrichard
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA. drebe003@umn.edu.
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. nahe0001@umn.edu.
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. jtian@unmc.edu.
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. mczimmerman@unmc.edu.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Zimmerman
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000628:therapy*; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011301:Preoptic Area / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000627:therapeutic use*; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D000804:Angiotensin II; D012964:Sodium; D013482:Superoxide Dismutase