[The effects of shRNA targeting angiotensin II type 1 receptor on blood pressure and AT1R mRNA expression in spontaneously hypertensive rats].
OBJECTIVE
To investigate the effects of retroviral vector containing shRNA targeting rat angiotensin II type 1 receptor (AT1R) gene (Ad5-AT1R-shRNA) on blood pressure and AT1R mRNA expression in spontaneously hypertensive rats (SHR).


METHODS
Retroviral vector containing shRNA targeting rat AT1R gene was constructed and propagated further in 293 cells. SHR rats were randomly divided into SHR + Ad5-AT1R-shRNA (1.7 x 10(9) TCID(50)/ml) group and SHR (Ad5-EGFP, 7.9 x 10(9) TCID(50)/ml, n = 11 each) and 11 male Wistar-Kyoto rats (WKY) serve as normal controls (Ad5-EGFP, 7.9 x 10(9) TCID(50)/ml). Systolic blood pressure was measured before and after single intravenous injection of Ad5-AT1R-shRNA or Ad5-EGFP. Heart, liver, kidney, aorta and adrenal gland were removed after blood pressure measurement. Tissue Ad5-AT1R-shRNA expression was detected with fluorescence microscope and AT1R mRNA in liver, kidney and aorta was measured by fluorescence quantitative PCR.


RESULTS
Ad5-AT1R-shRNA significantly reduced blood pressure compared with controls (-29 mm Hg, 1 mm Hg = 0.133 kPa, P < 0.05) 24 hours after single injection and this antihypertensive effect could last for 5 to 7 days. Ad5-AT1R-shRNA expression detected with fluorescence microscope was significantly increased in heart, liver, kidney, aorta and adrenal gland post Ad5-AT1R-shRNA injection. AT1R mRNA in kidney and aorta (0.086 +/- 0.014, 0.051 +/- 0.023) were significantly decreased in Ad5-AT1R-shRNA treated rats compared with SHR control rats (0.362 +/- 0.042, 0.463 +/- 0.045, P < 0.01).


CONCLUSIONS
The results indicate that Ad5-AT1R-shRNA could inhibit the tissue AT1R mRNA expression and produce prolonged antihypertensive effects in SHR rats.
Xiao
Chuan-Shi
CS
Department of Cardiology, Second Hospital of Shan Xi Medical University, Taiyuan 030001, China.
Zhang
Jin-Lian
JL
Qiu
Ling
L
D000256:Adenoviridae; D000818:Animals; D001794:Blood Pressure; D005822:Genetic Vectors; D006339:Heart Rate; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1