ACE-inhibition, but not weight reduction restores cardiomyocyte response to β-adrenergic stimulation in the metabolic syndrome

BMC Cardiovascular Disorders

Paul Herijgers¹  Kanigula Mubagwa¹  Karin R Sipido²  An Van den Bergh¹  Annelies Vanderper¹  Gerry Van der Mieren¹  Virginie Bito²  Ines Nevelsteen¹ 

[1] Department of Cardiovascular Sciences, Research Unit of Experimental Cardiac Surgery, KU Leuven, Herestraat 49, Leuven B-3000, Belgium;Research Unit of Experimental Cardiology, KU Leuven, Leuven, Belgium

关键词: ACE-inhibition;    Hypocaloric diet;    β-adrenergic stimulation;    Cardiomyocyte contractility;    Metabolic syndrome;   

Others  :  857587
DOI  :  10.1186/1471-2261-13-51

 received in 2013-03-03, accepted in 2013-07-10,  发布年份 2013

【 摘 要 】

Background

Diabetic cardiomyopathy is characterized by systolic and early diastolic ventricular dysfunction. In the metabolic syndrome (MS), ventricular stiffness is additionally increased in a later stage. It is unknown whether this is related to intrinsic cardiomyocyte dysfunction, extrinsic factors influencing cardiomyocyte contractility and/or cardiac function, or a combination of both. A first aim was to study cardiomyocyte contractility and Ca²⁺ handling in vitro in a mouse model of MS. A second aim was to investigate whether in vivo hypocaloric diet or ACE-inhibition (ACE-I) improved cardiomyocyte contractility in vitro, contractile reserve and Ca²⁺ handling.

Methods

This study was performed in LDL-receptor (LDLR−/−) and leptin-deficient (ob/ob), double knock-out mice (DKO), featuring obesity, type II diabetes, atherogenic dyslipidemia and hypertension. Single knock-out LDLR−/−, ob/ob and wild type mice were used as controls. Cellular contractility, Ca²⁺ handling and their response to in vivo treatment with diet or ACE-I were studied in isolated cardiomyocytes at baseline, during β-adrenergic stimulation or increased extracellular Ca²⁺, using field stimulation and patch-clamp.

Results

In untreated conditions, prolongation of contraction-relaxation cycle and altered Ca²⁺ handling are observed in MS. Response to increased extracellular Ca²⁺ and β-adrenergic stimulation is impaired and could not be rescued by weight loss. ACE-I restored impaired response to β-adrenergic stimulation in MS, but not the decreased response to increased extracellular Ca²⁺.

Conclusions

Cardiomyocyte contractility and β-adrenergic response are impaired in MS, due to alterations in cellular Ca²⁺ handling. ACE-I, but not weight loss, is able to restore cardiomyocyte response to β-adrenergic stimulation in MS.

【 授权许可】

   
2013 Nevelsteen et al.; licensee BioMed Central Ltd.

【 图 表 】

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