Leticia González

Publications (2)8.04 Total impact

• Source

  Available from: Sergio Lavandero

  Article: Rho kinase inhibition activates the homologous angiotensin-converting enzyme-angiotensin-(1-9) axis in experimental hypertension.

  María P Ocaranza, Paulina Rivera, Ulises Novoa, Melissa Pinto, Leticia González, Mario Chiong, Sergio Lavandero, Jorge E Jalil
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  ABSTRACT: Angiotensin II (Ang II) levels depend on renin, angiotensin-converting enzyme (ACE), and on the homologous angiotensin-converting enzyme (ACE2). Increased ACE and Ang II levels are associated with higher Rho kinase activity. However, the relationship between Rho kinase activation and ACE2 in hypertension is unknown. The role of the Rho kinase signaling pathway in both enzymatic activity and aortic gene expression of ACE2 in deoxycorticosterone acetate (DOCA) hypertensive rats was assessed in the present study. Compared with sham animals, Rho kinase activity was higher by 400% (P<0.05) in the aortic wall of the DOCA hypertensive rats. In addition to blood pressure reduction, the specific Rho kinase inhibitor fasudil reduced aortic Rho kinase activity to levels observed in the sham control group and increased ACE2 enzymatic activity (by 83% in plasma and by 52% in the aortic wall, P<0.05), ACE2, and endothelial nitric oxide synthase (eNOS) aortic mRNA levels (by 340 and 40%, respectively, P<0.05) with respect to the untreated hypertensive DOCA rats. Fasudil also increased significantly plasma levels of Ang-(1-9) in normotensive and in the hypertensive rats. Aortic mRNA and protein levels of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor 1 (PAI-1), and monocyte chemoattractant protein 1 (MCP-1) were significantly (P<0.05) higher in the untreated DOCA rats and were normalized by fasudil administration. In experimental hypertension, Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition reduces blood pressure and increases ACE2 levels and activity. At the same time, ROCK inhibition reduces angiotensin II and increases Ang-(1-9) plasma levels. Fasudil also increases vascular eNOS mRNA levels and reduces aortic overexpression of the remodeling promotion proteins TGF-β1, PAI-1, and MCP-1. This effect might additionally contribute to the antihypertensive and antiremodeling effects of ROCK inhibition in hypertension.
  Journal of hypertension 02/2011; 29(4):706-15. · 4.02 Impact Factor
• Article: Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro

  Maria Paz Ocaranza, Sergio Lavandero, Jorge E Jalil, Jaqueline Moya, Melissa Pinto, Ulises Novoa, Felipe Apablaza, Leticia González, Carol Hernández, Manuel Varas, René López, Iván Godoy, Hugo Verdejo, Mario Chiong
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  ABSTRACT: Background: Angiotensin-(1–9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown. Objective: To determine whether angiotensin-(1–9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin–angiotensin system. Methods and results: The administration of angiotensin-(1–9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1–9) was not modified with the simultaneous administration of the angiotensin-(1–7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 μmol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1–9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1–9) levels by several folds. Angiotensin-(1–9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction. Conclusion: Angiotensin-(1–9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.
  Journal of Hypertension 04/2010; 28(5):1054–1064. · 4.02 Impact Factor