Sex hormones regulate the renin angiotensin system. For example, estrogen enhances expression of the angiotensin type 2 receptor. We hypothesized that activation of the angiotensin type 2 receptor shifts the chronic pressure-natriuresis relationship leftward in females compared to males, and that this effect is lost with age. Mean arterial pressure was measured by radiotelemetry in adult (4 month old) and aged (14 month old) wild type and angiotensin type 2 receptor knockout male and female mice. Chronic pressure-natriuresis curves were constructed whilst mice were maintained on a normal salt (0.26 ) diet and following 6 days of high salt (5.0 ) diet. Mean arterial pressure was lower in adult wild type females than males (88+/-1 and 97+/-1 mmHg respectively), a difference that was maintained with age, but was absent in adult knockout mice. In wild-type females, the chronic pressure-natriuresis relationship was shifted leftward compared to knockout females, an effect that was lost with age. In males, the chronic pressure-natriuresis relationship was not influenced by angiotensin type 2 receptor deficiency. Compared to age-matched females, the chronic pressure-natriuresis relationships of male mice were shifted rightward. Renal expression of the angiotensin type 2 receptor was 4-fold greater in adult wild type females than males. With age, the angiotensin type 2 receptor to angiotensin type 1 receptor balance was reduced in females. Conversely, in males, angiotensin receptor expression did not vary significantly with age. In conclusion, the angiotensin type 2 receptor modulates the chronic pressure-natriuresis relationship in an age and sex-dependent manner.