Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

International Journal of Molecular Sciences

John P. Collister¹  Mitch Bellrichard¹  Donna Drebes¹  David Nahey¹  Jun Tian²  Matthew C. Zimmerman² 

[1] Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA; E-Mails:;Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; E-Mails:

关键词: superoxide dismutase (SOD);    median preoptic nucleus;    hypertension;    angiotensin II;    reactive oxygen species;    brain;    hypothalamus;   

DOI  :  10.3390/ijms151222203

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.