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

作者：MacIntyre Jessica N; Slusar Joanna E; Zhu Jiequan; Dong Alex X; Howlett Susan E^*; Kelly Melanie E

来源：Mechanisms of Ageing and Development, 2012, 133(9-10): 611-619.

DOI：10.1016/j.mad.2012.08.001

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

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 (%26gt;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 50 mM KCl and Ca2+ release by caffeine (10 mM) 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 10 nM ET-1 were inhibited by the ETA antagonist BQ-123 (1 mu M) in all groups. In contrast, the ETB antagonist BQ-788 (1 mu M) 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.