Mas-Mediated Antioxidant Effects Restore the Functionality of Angiotensin Converting Enzyme 2-Angiotensin-(1–7)-Mas Axis in Diabetic Rat Carotid
Figure 7
Conclusive graphical abstract. Endothelial AT1-activated NAD(P)H oxidase-driven generation of and H2O2 in carotid arteries from type I-diabetic rats impairs the functionality of the local vasoprotective ACE2-angiotensin-(1–7)-Mas axis, which in turn impairs carotid blood flow. In this mechanism, H2O2 derived from dismutation inhibits ACE2 activity in generating angiotensin-(1–7) by activating , while inhibits the nitrergic vasorelaxant effect evoked by angiotensin-(1–7) upon Mas receptors activation. The chronic treatment of diabetic rats with angiotensin-(1–7) restores the functionality of carotid ACE2-angiotensin-(1–7)-Mas axis by triggering a positive feedback on this axis, played by a residual population of endothelial Mas-receptors that blunts the endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species in rat carotid. Mas-mediated antioxidant effects evoked by the chronic treatment with angiotensin-(1–7) also restores carotid resistance and blood flow in diabetic rats, pointing the important contribution of the ACE2-angiotensin-(1–7)-Mas axis in maintaining carotid function.
