In this study, we designed to search for transcriptionally changed genes during human endothelial cell senescence at genome level and evaluate their contributions to vascular aging and hypertension in mouse models, and at the end, we demonstrate that NPRA is decreased with aging, which not only elevates blood pressure but also promotes endothelial cell senescence and vascular aging through PKG‐AMP‐activated protein kinase (AMPK)‐associated signaling axis. This evidence concerns the gene NPR1 and Hypertension.