Vasoprotective effects of neurocompensatory response to balloon injury during diabetes involve the improvement of Mas signaling by TGFβ1 activation

Carotid balloon injury in type I-diabetic rats leads to restenosis at the ipsilateral artery, which impairs the local Mas-mediated relaxation and the local blood flow. At the same time, carotid balloon injury in type I-diabetic rats triggers a neurocompensatory response at the contralateral carotid, where SP leads to the endothelial release of TGFβ1 by activating endothelial NK1 receptors. In turn, TGFβ1 activates ALK5 receptors, enhancing the expression and activity of muscular Nox4, which generates high concentrations of H2O2. This ROS acts as a relaxant factor that enhances the local Mas-mediated relaxation. As a vasoprotective mechanism, the enhanced relaxation mediated by Mas receptors restores the local blood flow, previously impaired by diabetes.71