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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Mas-Mediated Antioxidant Effects Restore the Functionality of Angiotensin Converting Enzyme 2-Angiotensin-(1-7)-Mas Axis in Diabetic Rat Carotid

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Pernomian, Larissa [1] ; Gomes, Mayara Santos [1] ; Araujo Restini, Carolina Baraldi [2] ; de Oliveira, Ana Maria [1]
Total Authors: 4
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Ribeirao Preto, Fac Med, BR-14096900 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Web of Science Citations: 9

We hypothesized that endothelial AT(1)-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1-7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1-7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1-7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II orangiotensin-(1-7) were obtained in carotid from streptozotocin-induced diabetic rats. Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid endothelial cells. Carotid flow was also determined. We found that endothelial AT1-activated NAD(P) H oxidase-driven generation of superoxide and hydrogen peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1-7)-Mas axis functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide derived from superoxide dismutation inhibits ACE2 activity in generating angiotensin-(1-7) seemingly by activating.. Cl, SWELL, while superoxide inhibits the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1-7). Angiotensin-(1-7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1-7)-Mas axis functionality by triggering a positive feedback played by endothelial Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species. Mas-mediated antioxidant effects also restored diabetic rat carotid flow, pointing to the contribution of ACE2-angiotensin-(1-7)-Mas axis in maintaining carotid flow. (AU)

FAPESP's process: 12/09019-3 - Consequences of dyslipidemia on the ACE - Ang II - AT1 and ACE2 - Ang-(1-7) - mas axes from the angiotensinergic system in aorta from young and adult LDLr knockout mice
Grantee:Ana Maria de Oliveira
Support type: Regular Research Grants
FAPESP's process: 09/01005-0 - Influence of oxidative stress on the response to angiotensin II in contralateral carotid of diabetic rat after balloon-catheter injury
Grantee:Larissa Pernomian
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/00640-7 - Study of the consequences of the inflammatory process induced by AT1 receptors during atherosclerosis on the ACE2 - angiotensin-(1-7) - Mas axis in mouse aorta and the involvement of Mas receptors in the vaso- and atheroprotective effects of losartan
Grantee:Larissa Pernomian
Support type: Scholarships in Brazil - Post-Doctorate