CONICET | Buscador de Institutos y Recursos Humanos

Full expression of Angiotensin II signaling in VSMCs is dependent on the ROS derived from NADPH oxidase and the dynamic association of the Ang II (Ang II) type I receptor (AT1R) with caveolae/lipid rafts.The chaperone Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. We examined the AT1 receptor antagonist Losartan effect, on Caveolin-1 and Hsp70 protein and its involvement on oxidative stress in VSMCs from SHR and WKY rats. VSMCs stimulated with Ang II (100 µmol/L) for 15 min in the presence or absence of Losartan (100 µmol/L) added 30 min before Ang II stimulation were subjected to RT-PCR and Western blot analysis. The exposure of SHR VSMCs to Ang II for 15 minutes downregulated membrane caveolin expression and overexpressed p22 and Nox4 NADHP oxidase isoforms, whereas Losartan increased Cav-1 expression, lightly increased Hsp70 and decreased p22 and Nox4 protein levels in SHR VSM cell membranes. VSMCs from WKY rats pretreated with Losartan 100 µmol/L and subsequently stimulated with Ang II (100 µmol/L) for 15 minutes decreased NADHP isoforms p22 and Nox4, and increased Hsp70 expression in cell membrane. Furthermore, Losartan abolished the phosphorylation of ERK1/2 that was induced by Ang II in SHR VSM cells. These findings suggest that after Losartan administration, translocation of Hsp70 to VSM cell membranes might exert a cytoprotective effect on oxidative stress.