Figure 5.

Effect of angiotensin (AII) on nuclear superoxide/H₂O₂ production, AT2 and PGC-1α mRNA expression. Treatment of isolated nuclei with AII increased the levels of nuclear superoxide/H₂O₂ (i.e., DHE fluorescence; a–d), which were inhibited by the simultaneous treatment with the AT1 receptor antagonist losartan (a; los), the antioxidant NAC and the Nox inhibitor DPI (b), but not by the AT2 receptor antagonist PD123,319 (PD) (a). Involvement of AT1 in these effects was confirmed by treatment of nuclei from AT1 and AT2 KO mice with AII, which also revealed an opposite effect of nuclear AT1 (increase) and AT2 (decrease) receptors on the levels of nuclear superoxide/H₂O₂ (c). The effects of AII on brain nuclei were also observed in nuclei from the MES 23.5 dopaminergic neuron cell line (d). However, the effects of AII on AT2 (e) and PGC-1α (f) mRNA expression were not inhibited by the antioxidant NAC or the Nox inhibitor DPI. Data are mean±S.E.M. *P<0.05 compared to control or WT (c), ^&compared to KO AT1, ^#P<0.05 compared to group treated with AII (a, b and d) or KO AT2 (c). One-way analysis of variance and Holm–Sidak post hoc test (n=4–10)