Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice

Détails

ID Serval
serval:BIB_B1F3F66E28B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice
Périodique
Journal of the Renin-Angiotensin-Aldosterone System
Auteur⸱e⸱s
Huggins  C. E., Domenighetti  A. A., Pedrazzini  T., Pepe  S., Delbridge  L. M.
ISSN
1470-3203 (Print)
Statut éditorial
Publié
Date de publication
09/2003
Volume
4
Numéro
3
Pages
186-90
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Résumé
INTRODUCTION: Angiotensin II (Ang II) is known to induce cardiac growth and modulate myocardial contractility. It has been reported that elevated levels of endogenous Ang II contribute to the development of cardiac hypertrophy in hypertensives. However, the long-term functional effects of cardiac exposure to Ang II in normotensives is unclear. A recently developed transgenic mouse (TG1306/1R), in which cardiac-specific overproduction of Ang II produces primary hypertrophy, provides a new experimental model for investigation of this phenotype. The aim of the present study was to use this model to investigate whether there is a functional deficit in primary hypertrophy that may predispose to cardiac failure and sudden death. We hypothesised that primary cardiac hypertrophy is associated with mechanical dysfunction in the basal state. METHODS: Normotensive heterozygous TG1306/1R mice harbouring multiple copies of a cardiac-specific rat angiotensinogen gene1 were studied at age 30-40 weeks and compared with age-matched wild-type littermates. Left ventricular function was measured ex vivo in bicarbonate buffer-perfused, Langendorff- mounted hearts (at a perfusion pressure of 80 mmHg, 37 degrees C) using a fluid-filled PVC balloon interfaced to a pressure transducer and digital data acquisition system. RESULTS: There was no difference in the mean (+SEM) intrinsic heart rate of TG1306/1R and wild-type control mice (357.4 +/- 11.8 vs. 367.5 +/- 20.9 bpm, n=9 & 7). Under standardised end-diastolic pressure conditions, TG1306/1R hearts exhibited a significant reduction in peak developed pressure (132.2 +/- 9.4 vs. 161.5 +/- 3.1 mmHg, n=9 & 7, p<0.05) and maximum rate of pressure development (3566.7 +/- 323.7 vs. 4486.3 +/- 109.4 mmHg, n=9 & 7, p<0.05). TG1306/1R mice show a significant correlation between incidence of arrhythmia and increasing heart size (Spearman s correlation coefficient 0.61). CONCLUSION: These data demonstrate that chronic in vivo exposure to elevated levels of intra-cardiac Ang II is associated with significant contractile abnormalities evident in the ex vivo intact heart. Our findings suggest that endogenous overproduction of cardiac Ang II, independent of changes in blood pressure, is sufficient to induce ventricular remodelling that culminates in impaired cardiac function which may precede failure.
Mots-clé
Angiotensin II/*metabolism Angiotensinogen/*genetics Animals Blood Pressure Cardiomegaly/etiology/*metabolism/*physiopathology Heart Rate Mice Mice, Transgenic Myocardial Contraction Myocardium/*metabolism Rats Tachycardia, Ventricular/metabolism/physiopathology Ventricular Remodeling
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 8:45
Dernière modification de la notice
20/08/2019 15:20
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