Abstract—Acute angiotensin II (Ang II) infusions into mice increase arterial pressure (AP) and elicit pressure natriuresis. We used this model of pressure natriuresis to delineate the distal nephron responses to AP-mediated increases in distal sodium delivery. In the first group, we measured changes in urinary sodium excretion (U_NaV) in male C57/BL6 anesthetized mice (n=9) before and during acute Ang II infusions (5 ng/g of body weight per minute). Acute Ang II infusions increased AP (98±3 to 126±5 mm Hg; P<0.001), urine flow (2.7±0.5 to 6.0±0.8 µL/min; P<0.01), and U_NaV (0.6±0.2 to 1.3±0.2 µEq/min; P<0.05). There were significant relationships between U_NaV and urine flow (y=0.207x+0.030; P<0.0001) and between U_NaV and AP (y=0.027x-2.100). In a separate series, distal sodium delivery and fractional reabsorption of distal sodium delivery were determined in control (n=12) and Ang II–infused mice (n=8) by comparing U_NaV before and after blockade of the 2 major distal nephron sodium transporters with amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight). A positive relationship was found between U_NaV (y=0.015x-1.100; P<0.0001) or distal sodium delivery (y=0.027x-0.900; P<0.0001) and AP. An inverse relationship was found between fractional reabsorption of distal sodium delivery and AP (y=-0.511x+128.300; P<0.01). These data indicate that Ang II–mediated pressure natriuresis involves an increase in distal sodium delivery combined with a reduced distal nephron fractional sodium reabsorption, suggesting that increased AP prevents the distal nephron transport mechanisms from accommodating the increased distal delivery.