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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2008, Vol. 2 Issue (1) : 19-24
Effects of RNA interference targeting angiotensin 1a receptor on blood pressure and cardiac hypertrophy of rats with renovascular hypertension
ZHANG Jingqun, SUN Honglei, MA Yexin, WANG Daowen
Department of Cardiology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
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Abstract The aim of this study is to investigate the effects of RNA interference (RNAi) targeting angiotensin 1a receptor (AT1a) on blood pressure and cardiac hypertrophy of rats with renovascular hypertension. Two RNAi plasmids, pAT1a-shRNA1 and pAT1a-shRNA2 each carrying a U6 promoter and an AT1a-specific shRNA-coding template sequence corresponding to the sites 928–946, 978–996 of the mRNA transcript, and a control plasmid pCon carrying a nonspecific shRNA-coding sequence were constructed. Thirty Sprague – Dawley rats with renovascular hypertension (2-kidney 1-clip) were randomly divided into 5 equal groups: Control group (without any intervention), pAT1a-shRNA1, pAT1a-shRNA2, pCon groups (with injection of the corresponding plasmid 4 mg/kg respectively into the tail vein), and valsartan group (30 mg/kg·d-1 by gavage). Three weeks after drug administration, pAT1a-shRNA1, pAT1a-shRNA2 and valsartan respectively resulted in decrease of the tail blood pressure by (15.1 ± 5.4), (16.4 ± 8.4) and (30.6 ± 18.2) mmHg. However, the tail blood pressure increased further by about 25 mmHg in both of pCon and control groups. The carotid artery pressures of pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups were all significantly lower than those of the control and pCon groups. The ratio of left ventricle weight to body weight (LV/BW) of the rats in pAT1a-shRNA1, pAT1a-shRNA2, and valsartan groups decreased significantly than in the control group (P < 0.01), similar to those of the normal SD rats(P > 0.05). Histopathological examination showed that the myocardiocytes were significantly hypertrophic and the basal membrane of the aorta was significantly thickened in the control group and such changes were alleviated in the pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups. Compared with the control group, pAT1a-shRNA1 and pAT1a-shRNA2 groups had lowered expression of AT1 receptor (in the myocardium and the thoracic aorta (all P < 0.01); however, there were no significant differences in expression levels of AT1 receptor in valsartan and the control groups (P > 0.05). We conclude that RNAi targeting AT1a receptor inhibits the development of renovascular hypertension and the accompanying cardiac hypertrophy. RNAi technology may become a new strategy of gene therapy for hypertension.
Issue Date: 05 March 2008
 Cite this article:   
SUN Honglei,ZHANG Jingqun,MA Yexin, et al. Effects of RNA interference targeting angiotensin 1a receptor on blood pressure and cardiac hypertrophy of rats with renovascular hypertension[J]. Front. Med., 2008, 2(1): 19-24.
1 Galli S M Phillips M I Angiotensin II AT (1A) receptorantisense lowers blood pressure in acute 2-kidney, 1-clip hypertensionHypertension 2001 38(3 Pt 2)674678
2 Peng J F Kimura B Fregly M J Phillips M I Reduction ofcold-induced hypertension by antisense oligodeoxynucleotides to angiotensinogenmRNA and AT1-receptor mRNA in brain and blood. Hypertension. 1998 31(6)13171323
3 Phillips M I Mohuczy-Dominiak D Coffey M Galli S M Kimura B Wu P Zelles T Prolonged reduction of highblood pressure with an in vivo, nonpathogenic, adeno-associated viralvector delivery of AT1-R mRNA antisenseHypertension 1997 29(1 Pt 2)374380
4 Elbashir S M Harborth J Lendeckel W Yalcin A Weber K Tuschl T Duplexesof 21-nucleotide RNAs mediate RNA interference in cultured mammaliancellsNature 2001 411(6836)494498
5 Pan D N Wei L Yao M Wan D F Gu J R Down-regulation of CT120A by RNA interferencesuppresses lung cancer cells growthZhonghuaYi Xue Za Zhi 2005 85(23)16011604(in Chinese)
6 Butticaz C Ciuffi A Muñoz M Thomas J Bridge A Pebernard S Iggo R Meylan P Telenti A Protection fromHIV-1 infection of primary CD4 T cells by CCR5 silencing is effectivefor the full spectrum of CCR5 expressionAntivir Ther 2003 8(5)373377
7 Giladi H Ketzinel-Gilad M Rivkin L Felig Y Nussbaum O Galun E Smallinterfering RNA inhibits hepatitis B virus replication in miceMol Ther 2003 8(5)769776
8 Wu Y Huang A L Tang N Zhang B Q Lu N F RNA interference inhibits replication andexpression of hepatitis B virus in miceZhonghua Yi Xue Za Zhi 2005 85(9)630634(in Chinese)
9 Ding H Schwarz D S Keene A Affar el B Fenton L Xia X Shi Y Zamore P D Xu Z Selective silencingby RNAi of a dominant allele that causes amyotrophic lateral sclerosisAging Cell 2003 2(4)209217
10 Brantl S Antisense-RNAregulation and RNA interferenceBiochimBiophys Acta 2002 1575(1–3)1525
11 Shan Z Z Dai S M Chen H Hypertension-associated left ventricular hypertrophy isrelated to the expression of cardiac proto-oncogene c-fosChinese J Pharmacol toxicolo 1998 12161165
12 Elbashir S M Martinez J Patkaniowska A Lendeckel W Tuschl T Functional anatomy of siRNAsfor mediating efficient RNAi in Drosophila melanogaster embryo lysateEMBO J 2001 20(23)68776888
13 Khvorova A Reynolds A Jayasena S D Functional siRNAs and miRNAs exhibit strand biasCell 2003 115(2)209216
14 Reynolds A Leake D Boese Q Scaringe S Marshall W S Khvorova A RationalsiRNA design for RNA interferenceNat Biotechnol 2004 22(3)326330
15 de Gasparo M Catt K J Inagami T Wright J W Unger T International union of pharmacology. XXIII.The angiotensin II receptors.PharmacolRev 2000 52(3)415472
16 Zhang J Q Ma Y X Wang D W Xiao J M Selective knockdownof Angiotensin II receptor subtype 1a in rat vascular smooth musclecells by RNA interferenceZhonghua Xin XueGuan Bing Za Zhi 2006 34(1)5459(in Chinese)
17 Goldblatt H Lynch J Hanzal R F Studies on experimental hypertension: production of persistentelevation of systolic blood pressure by means of renal ischemiaJ Exp Med 1934 59347379
18 Wiesel P Mazzolai L Nussberger J Pedrazzini T Twokidney, one clip and one-kidney, one clip hypertension in miceHypertension 1997 29(4)10251030
19 Cervenka L Horacek V Vaneckova I Hubacek J A Oliverio M I Coffman T M Navar L G Essential role of AT1A receptor in the development of 2K1C hypertensionHypertension 2002 40(5)735741
20 Hannon G J RNAinterferenceNature 2002 418(6894)244251
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