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ABSTRACT AIM: The renin-angiotensin system plays a crucial role in the development and establishment of hypertension, and the pharmacological blockade of the system results in a reduction in
blood pressure. In the present study, we investigated whether the effects of a novel, double-stranded, recombinant adeno-associated virus vector (rAAV)-mediated antisense angiotensin II
receptor 1 (AT1R) gene efficiently prevents the development of hypertension induced by a high-salt diet in adult, male Sprague-Dawley (SD) rats. METHODS: A rAAV was prepared with a cassette
containing a cytomegaloviruspromoter and partial cDNA (660 base pairs) for the AT1R inserted in the antisense direction (rAAV-AT1-AS). A single tail vein injection of the rAAV-AT1-AS or
rAAV-GFP (green fluorescent protein, a reporter gene) was performed in adult, male SD rats. Two weeks after injection, the animals were fed a diet containing 8% NaCl, and the systolic blood
pressure was measured weekly using the tail-cuff method for 12 weeks. RESULTS: The high-salt diet induced a significant rise in systolic blood pressure in the rAAV-GFP-treated animals;
however, the rAAV-AT1-AS treatment attenuated the rise in blood pressure (142.7±4.5 mmHg _vs_ 117±3.8 mmHg, _P_<0.01), and the hypotensive effect was maintained until the experiments
ended at 12 weeks. In the rAAV-GFP-treated animals AT1 was overexpressed in various tissues, especially in the aorta and kidney at mRNA levels; in contrast, rAAV-AT1-AS treatment markedly
attenuated AT1 expression. Further more, rAAV-AT1-AS treatment prevented target organ damages from hypertension, including cardiac dysfunction and renal injury compared to the rAAV-GFP
group. CONCLUSION: These results suggest that rAAV-mediated anti-AT1 delivery attenuates the development of hypertension and protects against renal injury and cardiac remodeling. SIMILAR
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Author notes * Xu-guang Li and Jiang-tao Yan: These authors contributed equally to this study. AUTHORS AND AFFILIATIONS * Institute of Hypertension and Department of Internal Medicine,
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China Xu-guang Li, Jiang-tao Yan, Xi-zheng Xu, Jia-ning Wang, Li-ming Cheng, Tao Wang,
Ping Zuo & Dao-wen Wang Authors * Xu-guang Li View author publications You can also search for this author inPubMed Google Scholar * Jiang-tao Yan View author publications You can also
search for this author inPubMed Google Scholar * Xi-zheng Xu View author publications You can also search for this author inPubMed Google Scholar * Jia-ning Wang View author publications You
can also search for this author inPubMed Google Scholar * Li-ming Cheng View author publications You can also search for this author inPubMed Google Scholar * Tao Wang View author
publications You can also search for this author inPubMed Google Scholar * Ping Zuo View author publications You can also search for this author inPubMed Google Scholar * Dao-wen Wang View
author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Dao-wen Wang. ADDITIONAL INFORMATION This work was supported by grants
from the National 863 Plan project (No 2004AA-217060), the National Basic Research “973” Program (No 2006CB503801), and the National Education Ministration project (No 20040487079). RIGHTS
AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, Xg., Yan, Jt., Xu, Xz. _et al._ Recombinant adeno-associated virus-mediated delivery of antisense
angiotensin II receptor 1 gene attenuates hypertension development. _Acta Pharmacol Sin_ 28, 1737–1745 (2007). https://doi.org/10.1111/j.1745-7254.2007.00676.x Download citation * Received:
11 June 2007 * Accepted: 24 June 2007 * Issue Date: 01 November 2007 * DOI: https://doi.org/10.1111/j.1745-7254.2007.00676.x SHARE THIS ARTICLE Anyone you share the following link with will
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content-sharing initiative KEYWORDS * hypertension * gene therapy * angiotensin II receptor 1 * antisense * double-stranded recombinant adeno-associated virus vector