Figure 6.

Proposed model of E2 effects involved in the regulation of vascular responses in ageing. Elderly females have less Ang-(1-7)-induced vasoprotective effects related to low levels of E2. To develop a mechanism to prevent increase in pressure levels, there is an increase in Mas receptor expression and its pathways in old females, for example, increased expression of SOD2/NRF-2/NOX2, a pathway involved in the control of the reactive oxygen species formation, which would be deleterious to the vessel. Despite these adaptive changes, vascular responsiveness remained inadequate in these females and upregulation of the Mas receptor axis was not able to overcome the deleterious effects induced by E2 absence. By replacing E2, there is a reversal of vascular nonresponsiveness to Ang-(1-7) and reestablishment of changes in Mas receptor and SOD2/NRF-2/NOX2 expression present in aorta from these old females. Ang-(1-7): angiotensin-(1-7); E2: estradiol; SOD: superoxide dismutase 2; NRF-2: nuclear factor erythroid 2-related factor 2; NOX2/gp91: isoform 2 from membrane-bound enzyme complex (NADPH).