Objectives: 

Previous studies have shown that Ang II is involved in the hypertension and renal changes secondary to an alteration in renal development. However, it is unknown whether the involvement of Ang II in these changes is sex- and/or ageing dependent. The aim of this study was to evaluate whether the role of Ang II in mediating the renal changes and hypertension secondary to an alteration in renal development is sex- and/or ageing-dependent.

Materials: 

Rats were treated with an AT1 receptor antagonist during nephrogenic period (ARAnp) and experiments performed at 3 and 10 months of age.

Results: 

ARAnp-treated rats were hypertensive but an age-dependent rise in blood pressure (BP) was only found in male rats. Candesartan treatment led to a fall of BP in ARAnp-treated rats but the fall was greater (P<0.05) in male (47 ± 7 mmHg) than in female (28 ± 5 mmHg) rats. An increase in oxidative stress is involved in the Ang II effects, since oxidated proteins are elevated in plasma and renal tissue in ARAnp rats (P<0.05) and pretreatment with tempol reduces (P<0.05) the fall in BP elicited by candesartan. Hypertension was not maintained by an elevation in plasma renin or AT1 receptor expression in mesenteric arteries and renal cortex since both parameters were similar to those found in control normotensive rats. Renal hemodynamic was significantly deteriorated during ageing in male but not in female ARAnp-treated rats. Renal hemodynamic response to Ang II was enhanced (P<0.05) in these male and female rats at 3 but not at 10 months of age.

Conclusions: 

These results suggest that oxidative stress mediates the involvement of Ang II in maintaining hypertension and renal changes when nephrogenesis is altered during renal development, and that this involvement is aging and sex-dependent but not secondary to an elevation in AT1 receptor expression or renal sensitivity to Ang II effects.