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

Abstract

Purpose: The 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). Methods: Fifty 18 month old male SHR were divided into two groups: control (CTL, n=25) and diabetic (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, hydroxyproline concentration, and gene expression of Atrial Natriuretic Peptide (ANP) and α- and β-Myosin Heavy Chain (MyHC) isoforms. 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. Results: DM group 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 (CTL: 193±34; DM: 201±36 mmHg). Echocardiography showed LV and left atrial dilation, LV diastolic and relative wall thickness decrease, and LV systolic and diastolic function impairment in DM. Papillary muscle study showed decreased myocardial contractility and contractile reserve in 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 (CTL: 1.00±0.38; DM: 1.88±0.69) and β/α-MyHC ratio (CTL: 1.20±0.60; DM: 2.26±0.94) were observed in DM. Conclusion: Diabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats. Support: CAPES and CNPq.