title: Dexamethasone alters vascular reactivity by enhancing COX-related vasodilatation in fetal ovine carotids.
abstract: Based on preliminary studies that contractile efficacy was altered in vertebral and basilar arteries from neonatal donors treated with postnatal glucocorticoids, we examined the hypothesis that postnatal dexamethasone (DEX), a glucocorticoid used for respiratory disease in neonates, can alter vascular reactivity. Using near-term fetal lamb carotids, we measured 5-hydroxytryptamine (5-HT) dose-response relationship in DEX-treated and untreated arteries. We found that DEX incubation for 1 h had no effect on 5-HT sensitivity and agonist affinity but significantly reduced 5-HT contractile efficacy, a response that became even more pronounced after 4 h of DEX treatment. Coincubation of DEX-treated arteries with INDO for 4 h reversed this DEX-induced attenuation in 5-HT contractile efficacy, although DEX had no significant effects on cyclooxygenase (COX)-1 and COX-2 protein abundance. This data suggests that DEX alters vascular reactivity through a COX-related mechanism, with possible repercussions to neurological injury.
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dangeles@llu.edu
authors.forename: Danilyn M
authors.initials: DM
authors.lastname: Angeles
authors.forename: Melody
authors.initials: M
authors.lastname: Chang
authors.forename: Valerie
authors.initials: V
authors.lastname: Leong
authors.forename: Kerby C
authors.initials: KC
authors.lastname: Oberg
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005333:Fetus; D006801:Humans; D007231:Infant, Newborn; D020768:Middle Cerebral Artery / Q000502:physiology; D012756:Sheep; D014664:Vasodilation / Q000502:physiology*
chemical_list: D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2