Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

Cardiovascular Diabetology

Original Investigation

Ana Angélica Henrique Fernandes¹  Natasha Priscilla Xavier²  Rodrigo Gimenes²  Camila Gimenes²  Paula Felippe Martinez²  Dijon Henrique Campos²  Marina Politi Okoshi²  Camila Moreno Rosa²  Marcelo Diarcadia Mariano Cezar²  Antonio Carlos Cicogna²  Katashi Okoshi³ 

[1] Department of Chemistry and Biochemistry, Institute of Biosciences, Sao Paulo State University, UNESP, Botucatu, Brazil;Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil;Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil;Departamento de Clinica Medica, Faculdade de Medicina de Botucatu, UNESP, Rubiao Junior, S/N 18618-970, Botucatu, SP, Brazil;

关键词: Diabetes mellitus;    Oxidative stress;    Systemic hypertension;    Spontaneously hypertensive rats;    Elderly;   

DOI  :  10.1186/1475-2840-12-152

 received in 2013-10-02, accepted in 2013-10-07,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe combination of systemic arterial hypertension and diabetes mellitus (DM) induces greater cardiac remodeling than either condition alone. However, this association has been poorly addressed in senescent rats. Therefore, this study aimed to analyze the influence of streptozotocin-induced DM on ventricular remodeling and oxidative stress in aged spontaneously hypertensive rats (SHR).MethodsFifty 18 month old male SHR were divided into two groups: control (SHR, n = 25) and diabetic (SHR-DM, n = 25). DM was induced by streptozotocin (40 mg/kg, i.p.). After nine weeks, the rats underwent echocardiography and myocardial functional study in left ventricular (LV) isolated papillary muscle preparations. LV samples were obtained to measure myocyte diameters, interstitial collagen fraction, and hydroxyproline concentration. Gene expression of atrial natriuretic peptide (ANP) and α- and β-myosin heavy chain (MyHC) isoforms was evaluated by RT-PCR. Serum oxidative stress was assessed by measuring lipid hydroperoxide concentration and superoxide dismutase and glutathione peroxidase activities. Statistics: Student’s t test or Mann-Whitney test, p < 0.05.ResultsSHR-DM presented higher blood glucose (487 ± 29 vs. 89.1 ± 21.1 mg/dL) and lower body weight (277 ± 26 vs. 339 ± 38 g). Systolic blood pressure did not differ between groups. Echocardiography showed LV and left atrial dilation, LV diastolic and relative wall thickness decrease, and LV systolic and diastolic function impairment in SHR-DM. Papillary muscle study showed decreased myocardial contractility and contractile reserve in SHR-DM. Myocyte diameters and myocardial interstitial collagen fraction and hydroxyproline concentration did not differ between groups. Increased serum pro-oxidant activity and gene expression of ANP and β/α-MyHC ratio were observed in DM.ConclusionDiabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats.

【 授权许可】

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© Rosa et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.