Age-associated alterations in retinal arteriole reactivity to endothelin-1 differ between the sexes
| Autor: | Jessica N. MacIntyre, Joanna E. Slusar, Alex X. Dong, Melanie E. M. Kelly, Jiequan Zhu, Susan E. Howlett |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Aging medicine.medical_specialty Intraocular pressure Endothelium Endothelin A Receptor Antagonists 030204 cardiovascular system & hematology Biology Peptides Cyclic Retina 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Piperidines Retinal Diseases Internal medicine medicine Animals 10. No inequality Antihypertensive Agents Sex Characteristics Endothelin-1 Microcirculation Antagonist Retinal Receptor Endothelin A Receptor Endothelin B Endothelin 1 Rats Inbred F344 Endothelin B Receptor Antagonists Rats Arterioles Endocrinology medicine.anatomical_structure chemistry Vasoconstriction cardiovascular system 030221 ophthalmology & optometry Female Endothelin receptor Caffeine Oligopeptides Perfusion Signal Transduction Developmental Biology |
| Zdroj: | Mechanisms of Ageing and Development. 133:611-619 |
| ISSN: | 0047-6374 |
| DOI: | 10.1016/j.mad.2012.08.001 |
| Popis: | 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 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 μM) in all groups. In contrast, the ETB antagonist BQ-788 (1 μM) 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. |
| Databáze: | OpenAIRE |
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