title: Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus.
abstract: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).
  
  
  
  Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney.
  
  
  
  Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.
  
  
  
  Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: C M
authors: CM
authors: Rosa
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: R
authors: R
authors: Gimenes
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: D H S
authors: DH
authors: Campos
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: G N
authors: GN
authors: Guirado
authors: Sagrado Coração University-USC, Bauru, Sao Paulo, Brazil.
authors: C
authors: C
authors: Gimenes
authors: Department of Chemistry and Biochemistry, Institute of Biosciences, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: A A H
authors: AA
authors: Fernandes
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: A C
authors: AC
authors: Cicogna
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: R M
authors: RM
authors: Queiroz
authors: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors: I
authors: I
authors: Falcão-Pires
authors: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors: D
authors: D
authors: Miranda-Silva
authors: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors: P
authors: P
authors: Rodrigues
authors: Department of Cardiopneumology, Medical School, Sao Paulo University-USP, Sao Paulo, Brazil.
authors: F R
authors: FR
authors: Laurindo
authors: Department of Cardiopneumology, Medical School, Sao Paulo University-USP, Sao Paulo, Brazil.
authors: D C
authors: DC
authors: Fernandes
authors: Department of Pathology, Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: C R
authors: CR
authors: Correa
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
authors: M P
authors: MP
authors: Okoshi
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil. katashi@fmb.unesp.br.
authors: K
authors: K
authors: Okoshi
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011918:Rats, Inbred SHR; D013311:Streptozocin; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D024061:Collagen Type III; D008054:Lipid Peroxides; D013311:Streptozocin; C056165:acetovanillone; D002374:Catalase; D005979:Glutathione Peroxidase
keywords: Myocardial fibrosis; NADPH oxidase; Oxidative stress; Spontaneously hypertensive rat; Systemic hypertension; Ventricular remodeling