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Revista chilena de cardiología

On-line version ISSN 0718-8560

Abstract

OCARANZA, María Paz et al. Lower tissue levels of homologous angiotensin I converting enzyme (ACE-2) and angiotensin 1-9 are associated to increased remodeling of the aortic wall of hypertensive rats. Rev Chil Cardiol [online]. 2010, vol.29, n.1, pp.69-82. ISSN 0718-8560.  http://dx.doi.org/10.4067/S0718-85602010000100007.

Background: In experimental models of myocardial infarction we have recently proposed a significant inter-regulation between levels of Angiotensin I converting enzyme (ACE) and its homologous, ACE-2; in addition, we have proposed that Angiotensin 1-9 (Ang-(1-9)) rather than Ang-(1-7) counter regulates Ang II. These relations have not been investigated in hypertensive aortic wall remodeling. Aim: To measure de expression of ACE and ACE-2, the aortic wall levels of Ang I, Ang II, Ang-(1-7) and Ang-(1-9), along with parameters of aortic wall remodeling in hypertensive rats. Methods: 18 Lewis rats were randomized to Goldblatt (2 kidneys, 1 clamped) induced hypertension (n=9) or sham operation (controls, n=9). Six weeks after surgery, relative cardiac mass (RCM), systolic blood pressure (SBP), medial layer aortic wall thickness (MLT) and ML área (MLA) were measured. The aortic wall levels of ACE and ACE-2, tissue growth factor ß(TGF- ß), plasminogen activator inhibitor (PAI-1) and monocyte chemoattractant protein (MCP-1) were determined by RT-PCR. Activity and protein levels of ACE and ACE-2 were measured by fluorometry and Western Blot and ANG I, Ang II, Ang-(1-7) and Ang-(1-9) levels were determined using HPLC and radioimmunoassay. Results: RCM and SBP increased significantly in hypertensive as opossed to sham operated rats. Hypertensive rats had a significant (p<0.05) increase in MLT (18%), MLA, (31%), mRNA levels of ACE (164%,), TGF-ß (105%,), PAI-1 (51%,) and MCP-1 (53%,). ACE and ACE-2 protein levels increased by 130 and 48%, respectively (p<0.05). All these effects were associated to a significant decrease in mRNA, protein levels and actiity of ACE-2 (-55%, -41%, and -54%, respectively, along with decreased aortic wall levels of Ang-(1-9) (-25%,). Levels of Ang 1-7 were not modified in hypertensive rats. Conclusion: these results strongly suggest that the aortic wall remodeling following experimentally induced hypertension is associated to interaction between ACE and ACE-2 and aortic wall levels of Ang II and Ang-(1-9), but not with those ofAng-(1-7).

Keywords : Homologous Angiotensin I converting Enzyme; angiotensin-(1-9); renin-angiotensin system.

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