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A potential role for angiotensin II in obesity induced cardiac hypertrophy and ischaemic/reperfusion injury

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Abstract

Background

The mechanisms for obesity induced myocardial remodelling and subsequent mechanical dysfunction are poorly understood. There is good evidence that angiotensin II and TNFα have strong growth promoting properties and are elevated with obesity. In addition, these two peptides may interact to exacerbate myocardial ischaemic/reperfusion injury.

Hypothesis

Obesity increases systemic and myocardial renin–angiotensin system (RAS) activity and TNFα levels and contributes to obesity induced cardiac remodelling and ischaemic/reperfusion injury.

Methods

Male Wistar rats were placed on a standard rat chow diet or cafeteria diet for 16 weeks. Two additional groups of rats received the respective diets and losartan (30 mg/ kg/d) in their drinking water. Hearts were perfused on the isolated working rat heart perfusion system and mechanical function was documented before and after 15 min normothermic total global ischaemia. Blood and myocardial samples were collected for angiotensin II, TNFα and NADPH oxidase activity determinations.

Results

The rats on the cafeteria diet became obese compared to rats on the standard rat chow (438 ± 5.9 g vs 393 ± 7.3 g for control, p < 0.05). Obesity was associated with elevated serum angiotensin II (0.050 ± 0.015 pmol/ml vs. 0.035 ± 0.003 pmol/ml, p < 0.05) and TNFα levels (42.8 ± 5.93 pg/ml vs. 13.18 ± 2.50 pg/ml, p < 0.05), and increased heart to body weight ratios (3.1 ± 0.04 mg/g vs. 2.8 ± 0.03 mg/g, p < 0.05). Losartan had no effect on body weight but decreased basal myocardial angiotensin II and TNFΑ levels as well as heart to body weight ratio in the obese and lean controls (2.5 ± 0.05 mg/g and 2.6 ± 0.04 mg/g relative to their controls, p < 0.05). Hearts from obese rats had lower reperfusion aortic outputs (AO) than their concurrent controls (18.42 ± 1.17 ml/min vs. 27.8 ± 0.83 ml/min, p < 0.05). Losartan improved aortic output recoveries in obese rats (23.0 ± 1.71 ml/min, p < 0.05).

Conclusions

Obesity increased serum angiotensin II and TNFα levels, blood pressure, and heart weight to body weight ratios. These changes were associated with decreased basal and post–ischaemic myocardial mechanical function. Chronic AT1 receptor antagonism prevented the adverse changes in heart weight, mechanical function and susceptibility to ischaemic/reperfusion injury. Although current data do not exclude additional mechanisms for obesity induced cardiac remodelling, they suggest that angiotensin II may contribute to obesity induced cardiac remodelling and ischaemic/reperfusion injury.

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Authors and Affiliations

  1. Department of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, 19063, Tygerberg 7505, South Africa

    E. F. du Toit, M. Nabben & A. Lochner

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  1. E. F. du Toit
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  2. M. Nabben
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  3. A. Lochner
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Correspondence to E. F. du Toit.

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du Toit, .F., Nabben, M. & Lochner, A. A potential role for angiotensin II in obesity induced cardiac hypertrophy and ischaemic/reperfusion injury. Basic Res Cardiol 100, 346–354 (2005). https://doi.org/10.1007/s00395-005-0528-5

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  • DOI: https://doi.org/10.1007/s00395-005-0528-5

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