title: Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats.
abstract: BACKGROUND
  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 (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.
  
  
  METHODS
  Student's t test or Mann-Whitney test, p < 0.05.
  
  
  RESULTS
  SHR-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.
  
  
  CONCLUSIONS
  Diabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats.
authors.forename: Camila Moreno
authors.initials: CM
authors.lastname: Rosa
authors.forename: Natasha Priscilla
authors.initials: NP
authors.lastname: Xavier
authors.forename: Dijon
authors.initials: D
authors.lastname: Henrique Campos
authors.forename: Ana Angélica Henrique
authors.initials: AA
authors.lastname: Fernandes
authors.forename: Marcelo Diarcadia Mariano
authors.initials: MD
authors.lastname: Cezar
authors.forename: Paula Felippe
authors.initials: PF
authors.lastname: Martinez
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Cicogna
authors.forename: Camila
authors.initials: C
authors.lastname: Gimenes
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gimenes
authors.forename: Marina Politi
authors.initials: MP
authors.lastname: Okoshi
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil. katashi@fmb.unesp.br.
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D004452:Echocardiography; D006909:Hydroxyproline / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D059467:Transcriptome; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
chemical_list: C000594638:MYH7 protein, rat; D009320:Atrial Natriuretic Factor; D024722:Cardiac Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D006909:Hydroxyproline