Age-associated alterations in retinal arteriole reactivity to endothelin-1 differ between the sexes

Jessica N. MacIntyre, Joanna E. Slusar, Jiequan Zhu, Alex X. Dong, Susan E. Howlett, Melanie E. Kelly

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Endothelin-1 (ET-1) is a vasoconstrictor implicated in age-related retinal pathologies. This study determined whether responses to ET-1 differed in retinal arterioles isolated from adult (2-3 months) and aged (>20 months) Fischer 344 rats of both sexes. Risk factors for retinal disease (retinal perfusion pressure, intraocular pressure, blood glucose) were not affected by age. However, sensitivity to ET-1 declined with age, especially in females. Vasoconstrictor responses to 50mM KCl and Ca2+ release by caffeine (10mM) were similar in all groups. Retinal ETA and ETB receptor expression also was similar in young and aged rats, regardless of sex. Contractions elicited by 10nM ET-1 were inhibited by the ETA antagonist BQ-123 (1μM) in all groups. In contrast, the ETB antagonist BQ-788 (1μM) restored ET-1-induced contractions in aged female vessels, but had no effect in any other group. Removal of the endothelium also restored contractions in vessels from aged females but not males. Thus, responsiveness to ET-1 declines with age in retinal microvasculature. In males, this is likely mediated by age-related changes in the ETA receptor signaling pathway. By contrast, effects of ET-1 on endothelial ETB receptors attenuate vasoconstrictor responses in aged females. © 2012 Elsevier Ireland Ltd.
    Original languageEnglish
    Pages (from-to)611-619
    Number of pages8
    JournalMechanisms of Ageing and Development
    Volume133
    Issue number9-10
    DOIs
    Publication statusPublished - Sep 2012

    Keywords

    • Aging
    • Endothelin receptors
    • Endothelium
    • Gender
    • Retinal microcirculation

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