title: Preserved endothelium-dependent dilatation of the coronary microvasculature at the early phase of diabetes mellitus despite the increased oxidative stress and depressed cardiac mechanical function ex vivo.
abstract: BACKGROUND
  There has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved.
  
  
  METHODS
  Zucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated.
  
  
  RESULTS
  Zucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels.
  
  
  CONCLUSIONS
  The presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart.
authors.affiliation: Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U1055, Université Joseph Fourier, BP 53, Grenoble cedex 09 F-38041, France. evangelia.mourmoura@ujf-grenoble.fr
authors.forename: Evangelia
authors.initials: E
authors.lastname: Mourmoura
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vial
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laillet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Rigaudière
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hininger-Favier
authors.forename: Hervé
authors.initials: H
authors.lastname: Dubouchaud
authors.forename: Beatrice
authors.initials: B
authors.lastname: Morio
authors.forename: Luc
authors.initials: L
authors.lastname: Demaison
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D008297:Male; D055806:Microvessels / Q000502:physiology*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology*