Fig. 3.

Physiologic compensatory mechanisms may be overwhelmed. Intracellular RAS may buffer the pro-oxidative effects of activation of plasma membrane AT1 receptors by extracellular Ang II. Internalization of the Ang II-AT1 complex to the nucleus, and activation of nuclear AT1 receptors by intracellular Ang II triggers a number of mechanisms that may protect cells against oxidative stress during the normal cell function (see Fig. 1, Fig. 2). However, excessive Ang II /AT1 activation or an increase in the AT1/AT2 ratio, as a result of disease-related mechanisms or aging, may overwhelm the compensatory mechanisms, leading to cell damage and progression of disease. Abbreviations: Ang II, angiotensin II; Ang 1-7, angiotensin 1-7; AT1, angiotensin type 1; AT2, angiotensin type 2; MAS, Mas receptors; ROS, reactive oxygen species. Images were produced using Servier Medical Art (http://www.servier.com).