Over-Expression of Copper-Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the RatReportar como inadecuado




Over-Expression of Copper-Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA

2

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA





*

Author to whom correspondence should be addressed.



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 pathways 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. View Full-Text

Keywords: superoxide dismutase SOD; median preoptic nucleus; hypertension; angiotensin II; reactive oxygen species; brain; hypothalamus superoxide dismutase SOD; median preoptic nucleus; hypertension; angiotensin II; reactive oxygen species; brain; hypothalamus





Autor: John P. Collister 1,* , Mitch Bellrichard 1, Donna Drebes 1, David Nahey 1, Jun Tian 2 and Matthew C. Zimmerman 2

Fuente: http://mdpi.com/



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