To confirm the pathogenic role of Erbb4-IR in the pathogenesis of hypertensive heart disease, we specifically knocked down cardiac Erbb4-IR by ultrasound-mediated Erbb4-IR shRNA-expressing plasmids and found that targeting cardiac Erbb4-IR blocked Ang II-induced hypertensive cardiac disease by increasing the LVEF and LVFS while reducing LV mass and inhibiting cardiac fibrosis. This evidence concerns the gene ERBB4 and hypertensive heart disease.