title: Effects of age and caloric restriction on the cardiac and coronary response to endothelin-1 in rats.
abstract: OBJECTIVE
  Aging is associated with alterations in the cardiovascular system such as increased vasoconstriction and decreased vasodilatation. Some of these changes are partially reversed by caloric restriction. Endothelin-1 is a potent vasoconstrictor which levels increased with age. The aim of this study is to analyze the role of endothelin-1 in the cardiac and coronary changes induced by age and whether these changes may be attenuated by a three-month caloric restriction.
  
  
  RESULTS
  Hearts from young (3 months old), aged (24 months old) and aged rats after 3 months of caloric restriction were perfused according to the Langendorff technique. Coronary vasoconstriction to endothelin-1 was reduced in old rats, and endothelin-1 increased myocardial contractility (dP/dt) and heart rate in old but not in young rats. These changes observed in old rats were partly reversed by caloric restriction. Also, in the myocardial tissue of old rats the gene expression of endothelin-1, inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-a) was increased, and the gene expression of endothelin ETB receptors and endothelial nitric oxide syntase (eNOS) was reduced, compared with young rats. Aging induced changes in the expression of ETB receptors and eNOS were reversed by caloric restriction.
  
  
  CONCLUSIONS
  These results suggest that aging produces alterations in myocardial and coronary responses to endothelin-1, that may be related to changes in expression of nitric oxide synthases and/or endothelin receptor subtypes, with some of these changes being prevented by caloric restriction.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: miriam.granado@uam.es.
authors.forename: Miriam
authors.initials: M
authors.lastname: Granado
authors.affiliation: Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Amor
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Monge
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Carreño-Tarragona
authors.affiliation: Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Carrascosa
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain.
authors.forename: Ángel Luis
authors.initials: ÁL
authors.lastname: García-Villalón
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction; D003326:Coronary Circulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019332:Endothelin-1 / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Age; Caloric restriction; Endothelin; Langendorff