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Reversible cardiac remodeling after renin‐angiotensin system stimulation in CYP1A1‐Ren2 transgenic rats
Author(s) -
Janssen Ben,
Heijnen Bart,
Pelkmans Leonie,
Danser Jan,
Garrelds Ingrid,
Mullins John,
De Mey Jo,
Struijker-Boudier Harry
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1135.3
Subject(s) - medicine , renin–angiotensin system , endocrinology , muscle hypertrophy , heart failure , hypertrophic cardiomyopathy , ventricular remodeling , cardiomyopathy , stimulation , blood pressure , cardiology
In transgenic inducible Cyp1a1‐Ren2 hypertensive rats (IHR) (pro)renin levels and blood pressure (BP) can be dose‐dependently titrated by administration of indole‐3‐carbinol (I3C). We examined if activation of (pro)renin to levels that cause severe hypertension (HT) would provoke hypertrophic cardiomyopathy or heart failure (HF). Echocardiographic studies in young and adult IHR revealed that stimulation of (pro)renin for 4 weeks (SBP>200mmHg) did not result in HF but incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness and decreased LV volume. Hypertrophic gene expression was upregulated, whereas activation of matricellular, inflammatory and fibrotic responses were absent. We tested also if this cardiac remodeling process could be reversed by de‐activation of the (pro)renin system. Four weeks after withdrawal of I3C, (pro)renin levels were normalized young and adult IHR. While in adult IHR BP returned to normal, HT was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin induced severe HT in IHR causes an age‐independent fully reversible myocardial concentric hypertrophic remodeling. In addition, de‐activation of the renin‐angiotensin system was sufficient for the reversion of cardiac hypertrophy, despite the presence of elevated BP.