title: NADPH oxidases are in part responsible for increased cardiovascular superoxide production during aging.
abstract: The aim of our study was to examine in rats, age-related differences in myocardial ischemic recovery and to determine the possible relationship with modification of cardiac and vascular oxidative stress. Isolated perfused hearts from young (2 months), adult (6 months), and old (21 months) Wistar rats were subjected to a ischemia-reperfusion sequence. Vascular histomorphological analyses were performed and NADPH oxidase was studied. The expression of angiotensin AT(1) receptors was evaluated using immunostaining. During the preischemic period, but also after ischemia, an aged-related decrease in myocardial functional parameters was observed, and was associated with an increased release of reactive oxygen species. In aortas, the activity and expression of NADPH oxidase increased with age according to the ESR, fluorescence microscopy, and immunohistochemistry; the NADPH oxidase involved was localized in endothelial cells. We found an age-related increase in the expression of endothelial angiotensin AT(1). Our study suggests that myocardial function and adaptation to ischemia-reperfusion declined during aging and are related to a higher level of oxidative stress. Endothelial NADPH oxidase is a major contributor to age-related cardiovascular deterioration. One of the regulators of vascular NADPH oxidase activity, the renin-angiotensin system, may be involved in the modulation of vascular superoxide production during the aging process.
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardio-vasculaires Expérimentales, IFR No. 100, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, BP 87900, 21079 Dijon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Oudot
authors.forename: Caroline
authors.initials: C
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Busseuil
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
authors.forename: Luc
authors.initials: L
authors.lastname: Demaison
authors.forename: Luc
authors.initials: L
authors.lastname: Rochette
mesh_terms: D000222:Adaptation, Physiological; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D002319:Cardiovascular System / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D004578:Electron Spin Resonance Spectroscopy; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004996:Ethidium / Q000031:analogs & derivatives / Q000032:analysis; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019255:NADPH Oxidases / Q000032:analysis / Q000378:metabolism*; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism*
chemical_list: C405009:1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidone; D011759:Pyrrolidines; D044140:Receptor, Angiotensin, Type 1; C067883:dihydroethidium; D013481:Superoxides; D019255:NADPH Oxidases; D004996:Ethidium