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Molecular determinants of (anti‐)hypertrophic cardiac remodeling in Cyp1A1‐Ren2 transgenic rats
Author(s) -
Janssen Ben,
van de Schans Veerle,
Smits Jos,
Blankesteijn Matthijs
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.21.6.a869-a
Background. When the aryl hydrocarbon, indole‐3‐carbinol (I3C), is added to the food of male transgenic Cyp1A1‐Ren2 rats, animals develop fulminant hypertension (systolic blood pressure >250 mmHg). The hypertension can be toggled off by withdrawal of the food additive. Here we studied the potential role of the anti‐hypertrophic mediator glycogen synthase kinase 3β (GSK‐3β) in cardiac remodeling 6 weeks after induction of hypertension (n=5) and 4 weeks after withdrawal of I3C when blood pressure (measured by tail cuff) was returned to control levels (n=4). Data were compared to rats not treated with I3C (n=5). Methods. Cardiac function and geometry was determined repeatedly by echocardiography (HP Sonos 5500). Left ventricular (LV) tissue was harvested and prepared to measure mRNA density of the hypertrophic markers ANF and β‐MHC as well as GSK‐3β activity (by Western blot and kinase assay). Results. In Cyp1A1‐Ren2 transgenic rats I3C induced hypertension was associated with concentric hypertrophic remodeling. End‐diastolic, systolic and stroke volumes decreased and LV wall thickness increased from 0.14 to 0.18 cm. Relative to controls ANF and β‐MHC mRNA expression levels were increased 10 and 2.5 times, respectively. GSKβ‐3 activity was significantly lowered (74±2 % of control). Following 4 weeks of withdrawal of I3C, echocardiographic parameters returned to values observed in non‐treated rats and was associated with a normalization of ANF, â‐MHC density, and GSK‐3â activity. Conclusion. Despite a 6 weeks fulminant hypertensive period, mechanisms of cardiac remodeling and regression were fully preserved in the inducible hypertensive rat.