title: Functional changes of the coronary microvasculature with aging regarding glucose tolerance, energy metabolism, and oxidative stress.
abstract: This study was aimed at characterizing the functional progression of the endothelial (ECs) and smooth muscle cells (SMCs) of the coronary microvasculature between youth and old age, as well as at determining the mechanisms of the observed changes on the basis of the glucose tolerance, mitochondrial energy metabolism, and oxidative stress. Male rats were divided into four age groups (3, 6, 11, and 17 months for the young (Y), young adult (YA), middle-aged (MA), and old (O) animals). The cardiac mechanical function, endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the coronary microvasculature were determined in a Langendorff preparation. The mitochondrial respiration and H2O2 production were evaluated and completed by ex vivo measurements of oxidative stress. EDD progressively decreased from youth to old age. The relaxation properties of the SMCs, although high in the Y rats, decreased drastically between youth and young adulthood and stabilized thereafter, paralleling the reduction of mitochondrial oxidative phosphorylation. The ECs dilatation activity, low at youth, was stimulated in YA animals and returned to their initial level at middle age. That parameter followed faithfully the progression of the amount of active cardiac endothelial nitric oxide synthase and whole body glucose intolerance. In conclusion, the progressive decrease in EDD occurring with aging is due to different functional behaviors of the ECs and SMCs, which appear to be associated with the systemic glucose intolerance and cardiac energy metabolism.
authors.affiliation: Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U1055, Université Joseph Fourier, BP 53, 38041, Grenoble cedex 09, France.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Mourmoura
authors.forename: Karine
authors.initials: K
authors.lastname: Couturier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hininger-Favier
authors.forename: Corinne
authors.initials: C
authors.lastname: Malpuech-Brugère
authors.forename: Kasra
authors.initials: K
authors.lastname: Azarnoush
authors.forename: Melanie
authors.initials: M
authors.lastname: Richardson
authors.forename: Luc
authors.initials: L
authors.lastname: Demaison
mesh_terms: D000375:Aging; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D008297:Male; D008833:Microcirculation; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*
chemical_list: D005947:Glucose