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Deoxycorticosterone acetate-salt mice exhibit blood pressure-independent sexual dimorphism

Item Type:Article
Title:Deoxycorticosterone acetate-salt mice exhibit blood pressure-independent sexual dimorphism
Creators Name:Karatas, A. and Hegner, B. and de Windt, L.J. and Luft, F.C. and Schubert, C. and Gross, V. and Akashi, Y.J. and Guergen, D. and Kintscher, U. and da Costa Goncalves, A.C. and Regitz-Zagrosek, V. and Dragun, D.
Abstract:We tested the hypothesis that female and male mice differ in terms of cardiac hypertrophy after deoxycorticosterone acetate (DOCA)+salt hypertension (uninephrectomy and 1% saline in drinking water) and focused on calcineurin signaling. We excluded confounding effects of blood pressure elevation or sex-related blood pressure differences by treating DOCA-salt mice with hydralazine (250 mg/L in drinking water). We found that directly measured mean arterial blood pressure was lowered to control values with hydralazine and corroborated this finding in separate mouse groups with radiotelemetry. Male mice were more responsive to DOCA-salt-related effects. They developed more left ventricular hypertrophy and more renal hypertrophy after 6 weeks of DOCA-salt+hydralazine compared with female mice. In hearts, transcripts for calcineurin Abeta and for myocyte-enriched calcineurin interacting protein 1 were upregulated in male but not in female mice. Enhanced activity of calcineurin Abeta, as indicated by diminished phosphorylation of NFATc2 in male mice, accounted for this sex-specific difference. Stretch-related, inflammatory, and profibrotic responses were also accentuated in male mice, as shown by higher transcript levels of atrial natriuretic peptide, monocyte chemoattractant protein-1, and transforming growth factor-beta. Our results support sex-specific regulation of the calcineurin pathway in response to largely blood pressure-independent mineralocorticoid action. We suggest that sex-specific calcineurin activation determines the maladaptive cardiac and renal hypertrophic responses and accompanying organ injury in male mice.
Keywords:Heart, Kidney, Hypertrophy, Inflammation, Fibrosis, Calcineurin, MCIP1, NFATc2, Animals, Mice
Publisher:American Heart Association
Page Range:1177-1183
Date:April 2008
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.107.107938
PubMed:View item in PubMed

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