Characterization of renin-angiotensin system in cardiomyopathy induced by sympathetic hyperactivity

Author(s)

Julio Cesar Batista Ferreira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2006-12-08

Examining board members

Patricia Chakur Brum; Maria Luiza Morais Barreto de Chaves; Edilamar Menezes de Oliveira

• Advisor: Patricia Chakur Brum

Abstract

We have recently reported that disruption of both \'alfa\' 2A and \'alfa\' 2C adrenergic receptor subtypes (KO) in mice leads to sympathetic hyperactivity with evidence of heart failure (HF) by seven months (mo) of age. In the present study, we have performed the phenotypical characterization on KO mice at three and seven month of age. In addition, we evaluated the effect of sympathetic hyperactivity on cardiac renin-angiotensin system (RAS) components. For that, we evaluated cardiac Ang II content, angiotensin converting activity (ACE), plasma renin activity and cardiac angiotensinogen expression. At three mo, KO mice displayed reduced fractional shortening (16%) and increased cardiomyocyte width compared with age-matched wild type (WT). Indeed, KO mice showed significantly increased cardiac Ang II content, cardiac ACE activity, angiotensinogen expression and plasma renin activity. At seven mo, KO mice displayed exercise intolerance, reduced fractional shortening (34%), cardiac dilatation, lung edema, increased cardiomyocyte width and increased cardiac collagen content compared with age-matched WT. In addition, KO mice presented an increased cardiac Ang II content and angiotensinogen expression, concomitantly with a decreased plasma renin activity. Collectively, these results uncover potential feedback regulation of cardiac and circulating components of SNS and RAS, which may contribute to a better understanding of the processes taking place during the progression of cardiomyopathy induced by sympathetic hyperactivit. (AU)

• FAPESP's process: 04/04042-0 - Characterization of the renin-angiotensin system involvement in sympathetic hyperactivity-induced cardiomyopathy
• Grantee: Julio Cesar Batista Ferreira
• Support Opportunities: Scholarships in Brazil - Master