MAS-mediated antioxidant effects restore the functionality of angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid.
Biomed Res Int
; 2014: 640329, 2014.
Article
em En
| MEDLINE
| ID: mdl-24877125
ABSTRACT
We hypothesized that endothelial AT1-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 or angiotensin-(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 I(Cl,SWELL0, 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.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Angiotensina I
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Artérias Carótidas
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Proteínas Proto-Oncogênicas
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Peptidil Dipeptidase A
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Receptores Acoplados a Proteínas G
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Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 1
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Antioxidantes
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article