Enalapril and nifedipine are used as antihypertensive drugs; however, the therapeutic target molecules regulated by enalapril and nifedipine have yet to be fully identified. The aim of this study was to identify novel target genes that are specifically regulated by enalapril and nifedipine in tissues from spontaneously hypertensive rats (SHR) using DNA microarray analysis. We found that administration of SHR with enalapril and nifedipine differentially regulated 33 genes involved in the pathogenesis of cardiovascular diseases. Furthermore, we identified 16 genes that have not previously been implicated in cardiovascular diseases, including interleukin-24 (IL-24). Among them, exogenous administration of IL-24 attenuated the expression of vascular inflammation and hypertension-related genes induced by H2O2 treatment in mouse vascular smooth muscle (MOVAS) cells. This study provides valuable information for the development of novel antihypertensive drugs. In addition, the genes identified may be of use as biomarkers and therapeutic targets for cardiovascular diseases, including hypertension.