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SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats

  • Molecular and Cellular Mechanisms of Disease
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Excessive sympathetic activity contributes to the initiation and progression of hypertension. Reactive oxygen species in the paraventricular nucleus (PVN) is involved in sympathetic overdrive and hypertension. The present study was designed to investigate whether superoxide dismutase 1 (SOD1) overexpression in the PVN attenuated sympathetic activation and hypertension. Adenoviral vectors containing human SOD1 or null adenoviral vectors were microinjected into the PVN of Wistar rats and spontaneously hypertensive rats (SHR). Significant depressor effects were observed from weeks 1 to 4 after SOD1 gene transfer in SHR. Acute experiments were carried out at the end of the 3rd week. In the PVN, superoxide anion and angiotensin II levels were increased while SOD1 activity and protein expression were decreased in SHR, which were attenuated by SOD1 overexpression in the PVN. However, SOD1 overexpression had no significant effect on the SOD2 activity in the PVN. The blood pressure response to ganglionic blockade, cardiac sympathetic nerve activity, and cardiac sympathetic afferent reflex (CSAR) were enhanced, and the plasma norepinephrine level was increased in SHR, which were prevented by SOD1 gene transfer in the PVN. Furthermore, SOD1 overexpression decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocardial cells, media thickness, and the media/lumen ratio of small arteries in the heart in SHR. These results indicate that SOD1 overexpression in the PVN reduces arterial blood pressure, attenuates excessive sympathetic activity and CSAR, and improves myocardial and vascular remodeling in SHR.

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Acknowledgments

This work was supported by the Chinese National Natural Science Foundation (31171095, 31271213, and 30870908), Science and Technology Foundation from Nanjing Medical University (09NJMUZ04), Natural Science Foundation from the Department of Education of Jiangsu Province (10KJB310004), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China

    Ning Yuan, Feng Zhang, Ling-Li Zhang, Juan Gao, Ye-Bo Zhou, Ying Han & Guo-Qing Zhu

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  1. Ning Yuan
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  2. Feng Zhang
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  3. Ling-Li Zhang
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Correspondence to Guo-Qing Zhu.

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Ning Yuan and Feng Zhang contributed equally to this work.

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Yuan, N., Zhang, F., Zhang, LL. et al. SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats. Pflugers Arch - Eur J Physiol 465, 261–270 (2013). https://doi.org/10.1007/s00424-012-1173-0

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  • DOI: https://doi.org/10.1007/s00424-012-1173-0

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