Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

Niklas Klatt, Katharina Scherschel, Claudia Schad, Denise Lau, Aline Reitmeier, Pawel Kuklik, Kai Muellerleile, Jin Yamamura, Tanja Zeller, Daniel Steven, Stephan Baldus, Benjamin Schäffer, Christiane Jungen, Christian Eickholt, Katharina Wassilew, Edzard Schwedhelm, Stephan Willems, Christian Meyer

9 Citationer (Scopus)

Abstract

Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (P = 0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II-treated animals compared to the control group (18 ± 4 mm vs. 13 ± 2 mm, respectively, P = 0.002). However, ANG II-treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high-sensitivity C-reactive protein and urinary 8-iso-prostaglandin F2α were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep.

OriginalsprogEngelsk
TidsskriftPhysiological Reports
Vol/bind4
Udgave nummer17
Sider (fra-til)e12897
DOI
StatusUdgivet - sep. 2016

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