The beginning of this trend was based on experimental observations that transgenic rodent models with hypertension, such as spontaneously hypertensive rats (SHR) tend to exhibit varying degrees of cardiac fibrosis (41), and further evolved into dissection of the role of major components of RAS (e.g., AngII, aldosterone) (87, 88) and suppressed endothelium-derived nitric oxide (NO) synthesis (89) in the pathogenesis of cardiac fibrosis. Here, AGT is linked to hypertensive disorder.