Aim RNA interference was used to downregulate angiotensin converting enzyme (ACE) and angiotensinⅡtype 1 receptor (AT1R), and to observe its effects on blood pressure and brain tissue injury in spontaneously hypertensive rats (SHR). Methods SHR was randomly divided into 5 groups:blank control group, virus control group, Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group, Ad5-ACE-AT1R-shRNA treatment group, and WKY normal blood pressure control group was set up. All rats in each group were injected 1 time in the first and seventeenth day of the experiment. On the third day after the first injection, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of ACE and Ang Ⅱ in rat brain, real-time fluorescent quantitative PCR was used to detect the expression of ACE mRNA and AT1R mRNA in brain tissue, Western blot was used to detect the expression of ACE and AT1R protein in brain tissue. At the end of the experiment, brain tissue was examined by light microscopy to observe the brain structure. Results On the third day after the first injection, the tail arterial pressure of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group decreased by 25.2±5.3 mmHg, 23.5±4.8 mmHg and 27.1±6.4 mmHg, 24.4±5.6 mmHg, 23.6±4.9 mmHg and 26.3±6.9 mmHg respectively on the 14th day, and the blood pressure rose on the 17th day after Ad5-ACE-shRNA treatment and Ad5-AT1R-shRNA treatment after the second injection The tail arterial pressure of Ad5-ACE-AT1R-shRNA treatment group decreased again. On the 23rd day, the arterial pressure decreased by 40.2±4.5 mmHg, 37.8±3.9 mmHg and 43.7±7.3 mmHg respectively before the first injection. On the 37th day, The blood pressure rose to the level before the second injection on the 40th day. The blood pressure of the blank control group and the virus control group continued to increase by 26 mmHg, there was no significant difference between the two groups; the tail arterial pressure of the normal blood pressure control group had no obvious change. The expression of ACE mRNA in brain tissue of Ad5-ACE-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group and the expression of AT1R mRNA in the brain tissue of Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group were significantly lower than those of blank control group and virus control group (P＜0.05), but there was no significant difference compared with normal blood pressure control group. The expression of AT1R protein in brain tissue of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group was significantly lower than that of blank control group and virus control group (P＜0.05). The light microscope showed that the brain tissue structure of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group was significantly improved.Conclusion RNA interference downregulated ACE and AT1R expression, reduced blood pressure in spontaneously hypertensive rats and improved brain injury, especially Ad5-ACE-AT1R-shRNA treatment had obvious effect and less side effect. RNA interference has a good application prospect for gene therapy of hypertension.