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Hypertension is a global health problem. It has been reported that acupuncture at Taichong acupoints (LR3) decreases high blood pressure in spontaneously hypertensive rats. A transcriptome analysis can profile gene expression and its relationship with acupuncture. In this study, rats were treated with 2 weeks of acupuncture followed by regular recording of blood pressure (BP). The mRNA changes in the rostral ventrolateral medulla (RVLM) were evaluated to uncover the genetic mechanisms of acupuncture by using a whole transcript array (Affymetrix Rat Gene 1.0 ST array). BP measurements showed that acupuncture significantly decreased systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR). In the bioinformatics results, 2371 differentially expressed genes (DEGs) were identified, where 83 DEGs were overlapped among Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and SHRs + acupuncture rats (SHRs+Acu). Gene ontology (GO) and pathway analysis revealed that 279 GO terms and 20 pathways with significant differences were related to oxidative stress, inflammation, and vascular endothelial function. In addition, coexpressed DEGs networks indicated that Cd4 and Il-33 might mediate the cascade of inflammation and oxidative stress responses, which could serve as a potential target of acupuncture treatment. In conclusion, our study demonstrated that acupuncture is a promising therapy for treating hypertension and could regulate multiple biological processes mainly involving oxidative stress, inflammation, and vascular endothelial function. [ABSTRACT FROM AUTHOR]