title: Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles.
abstract: OBJECTIVE
  The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific.
  
  
  METHODS
  Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling.
  
  
  RESULTS
  In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors.
  
  
  CONCLUSIONS
  Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, School of Medicine, West Virginia University, Morgantown, WV, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Leblanc
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Dougherty
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Reyes
authors.forename: Robert D
authors.initials: RD
authors.lastname: Shipley
authors.forename: Donna H
authors.initials: DH
authors.lastname: Korzick
authors.forename: Judy M
authors.initials: JM
authors.lastname: Muller-Delp
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001160:Arterioles; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017466:Receptors, Endothelin / Q000378:metabolism*; D012727:Sex Characteristics; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D016232:Endothelins; D017466:Receptors, Endothelin