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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/R26    most recent 00424.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ferreira, J. C. B. Articles by Brum, P. C. Search for Related Content PubMed PubMed Citation Articles by Ferreira, J. C. B. Articles by Brum, P. C.

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Control Mechanisms of Renin Synthesis and Release: A 21st Century Perspective

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

¹School of Physical Education and Sport, and ²Heart Institute (InCor), Medical School, University of São Paulo, and ³Nephrology Division, Federal University of Sao Paulo State, São Paulo, Brazil

Submitted 15 June 2007 ; accepted in final form 29 October 2007

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 _2A and _2C adrenoceptor knockout (_2A/_2CARKO) 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, _2A/_2CARKO 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, _2A/_2CARKO 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 AT₁ 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.

sympathetic nervous system; AT₁ receptor blocker; _2a/_2c adrenergic knockout mice