The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Author Ferreira, J. C. B. Google Scholar
Bacurau, A. V. Google Scholar
Evangelista, F. S. Google Scholar
Coelho, M. A. Google Scholar
Oliveira, E. M. Google Scholar
Casarini, D. E. Autor UNIFESP Google Scholar
Krieger, J. E. Google Scholar
Brum, P. C. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. the role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C) ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. in addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). in contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.
Keywords sympathetic nervous system
AT(1) receptor blocker
alpha(2a)/alpha(2c) adrenergic knockout mice
Language English
Date 2008-01-01
Published in American Journal of Physiology-regulatory Integrative and Comparative Physiology. Bethesda: Amer Physiological Soc, v. 294, n. 1, p. R26-R32, 2008.
ISSN 0363-6119 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent R26-R32
Origin http://dx.doi.org/10.1152/ajpregu.00424.2007
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000252243800004
URI http://repositorio.unifesp.br/handle/11600/30238

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