Angiotensin-(1-9) reduces hypertension, ameliorates structural alterations (hypertrophy and fibrosis), oxidative stress in the heart and aorta and improves cardiac and endothelial function in hypertensive rats. These effects were mediated by the AT2 receptor but not by the angiotensin-(1-7)/Mas receptor axis.
Menores niveles tisulares de la enzima convertidora de angiotensina I homóloga (eca-2) y angiotensina-(1-9) están asociados a mayor remodelamiento de la pared aórtica de ratas hipertensas
background: The angiotensin converting enzyme (ACE) gene polymorphism determines increased ACE activity and angiotensin (Ang) II levels in Brown Norway rats (BN), compared to Lewis rats (LL). Similar polymorphism has been described in humans. ACE2 through Ang-(1-9) rather than Ang-(1-7) counteracts the deleterious effects of Ang II. It is unknown whether the ACE polymorphism counteracts the ECA2/Ang1-9 axis and determines increased remodeling of the aortic wall in hypertensive rats. Objective: To determine the effects of ACE gene polymorphism in the ECA2/Ang1-9 axis activity and its impact on the aortic wall remodeling secondary to hypertension (HT). Methods: Male homozygous rats BN and LL were used. Hypertension was induced by the Goldblatt procedure (GB, 2 K-1clip). Pseudo-operated rats were used as controls (Sham). At 6 weeks after surgery, we determined the body weight (BW) and systolic blood pressure (SBP). In aorta, we determined the ACE and ACE2 activities, Ang II/Ang1-9 levels, protein expression of collagen type I, positive cells for ED-1 inflammatory cells and medial thickness (MT) and area (MA) of aortic wall. Results: ACE polymorphism with higher levels of ACE and Ang II determined a significant decrease of ACE2 activity, Ang-(1-9) levels and aortic wall remodeling in normotensives and hypertensives rats. Conclusion: ACE polymorphism with increased ACE activity and AngII levels determines a significant inter-regulation between ACE/AngII and ACE2/Ang-(1-9) axis which is associated with increased remodeling of the aortic wall. Fondecyt 1100874.
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