Aim:The renin-angiotensin system plays a crucial role in the development andestablishment of hypertension,and the pharmacological blockade of the systemresults in a reduction in blood pressure.In the present study,we investigatedwhether the effects of a novel,double-stranded,recombinant adeno-associatedvirus vector (rAAV)-mediated antisense angiotensin Ⅱ receptor 1 (AT_1R) geneefficiently prevents the development of hypertension induced by a high-salt dietin adult,male Sprague-Dawley (SD) rats.Methods:A rAAV was prepared with acassette containing a cytomegalovirus promoter and partial cDNA (660 base pairs)for the AT_1R inserted in the antisense direction (rAAV-AT_1-AS).A single tail veininjection of the rAAV-AT_1-AS or rAAV-GFP (green fluorescent protein,a reportergene) was performed in adult,male SD rats.Two weeks after injection,the animalswere fed a diet containing 8% NaCl,and the systolic blood pressure was measuredweekly using the tail-cuff method for 12 weeks.Results:The high-salt dietinduced a significant rise in systolic blood pressure in the rAAV-GFP-treatedanimals;however,the rAAV-AT_1-AS treatment attenuated the rise in blood pres-sure (142.7±4.5 mmHg vs 117±3.8 mmHg,P<0.01),and the hypotensive effect wasmaintained until the experiments ended at 12 weeks.In the rAAV-GFP-treatedanimals AT_1 was overexpressed in various tissues,especially in the aorta andkidney at mRNA levels;in contrast,rAAV-AT_1-AS treatment markedly attenuatedAT_1 expression.Furthermore,rAAV-AT_1-AS treatment prevented target organdamages from hypertension,including cardiac dysfunction and renal injury com-pared to the rAAV-GFP group.Conclusion:These results suggest that rAAV-mediated anti-AT_1 delivery attenuates the development of hypertension and pro-tects against renal injury and cardiac remodeling. Aim: The renin-angiotensin system plays a crucial role in the development andestablishment of hypertension, and the pharmacological blockade of the system results in a reduction in blood pressure. The current study, we investigatedwhether the effects of a novel, double-stranded, recombinant adeno-associated virus vector (rAAV) genetically resistant to angiotensin II receptor 1 (AT 1 R) geneefficiently prevents the development of hypertension induced by a high-salt dietin adult, male Sprague-Dawley (SD) rats. Methods: A rAAV was prepared with acassette containing a cytomegalovirus promoter and partial cDNA (660 base pairs) for the AT_1R inserted in the antisense direction (rAAV-AT_1-AS). A single tail vein injection of the rAAV-AT_1- AS or rAAV-GFP (a reporter gene) was performed in adult, male SD rats. Two weeks after injection, the animalswere 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-s However, the rAAV-AT_1-AS treatment attenuated the rise in blood pres-sure (142.7 ± 4.5 mmHg vs 117 ± 3.8 mmHg, P <0.01), while the rAAV- and the hypotensive effect was maintained until the experiments ended at 12 weeks. The rAAV-GFP-treated animals AT_1 was overexpressed in various tissues, especially in the aorta and kidney at mRNA levels; in contrast, rAAV-AT 1-AS treatment markedly attenuated AT-1 expression. , rAAV-AT_1-AS treatment prevented target organdamages from hypertension, including cardiac dysfunction and renal injury com-pared to the rAAV-GFP group. Confc: These results suggest that rAAV-mediated anti-AT_1 delivery attenuates the development of hypertension and pro- tects against renal injury and cardiac remodeling