In mice, the augmented urinary excretion of the renin substrate, angiotensinogen (AGT), positively correlates with renal Ang II concentration and increases systolic blood pressure, but not plasma Ang II (Kurtz and Wagner, 1998; Kobori et al., 2002, 2003), supporting the concept that intratubular RAS activation contributes to the pathogenesis of hypertension. The gene discussed is REN; the disease is hypertensive disorder.