title: Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebral arteries.
abstract: In the newborn, cyclooxygenase (COX)-derived products play an important role in the cerebrovascular dysfunction after ischemia-reperfusion (I/R). We examined effects of I/R on expression of COX-1 and COX-2 isoforms in large cerebral arteries of anesthetized piglets. The circle of Willis, the basilar, and the middle cerebral arteries were collected from piglets at 0.5-12 h after global ischemia (2.5-10 min, n = 50), hypoxia (n = 3), or hypercapnia (n = 2) and from time-control (n = 19) or untreated animals (n = 7). Tissues were analyzed for COX-1 and COX-2 mRNA and protein using RNase protection assay and immunoblot analysis, respectively. Ischemia increased COX-2 mRNA by 30 min, and maximal levels were reached at 2 h. Hypoxia or hypercapnia had minimal effects on COX-2 mRNA. COX-2 protein levels were also consistently elevated by 8 h after I/R. Increases in COX-2 mRNA or protein were not influenced by pretreatment with either indomethacin (5 mg/kg iv, n = 5) or nitro-L-arginine methyl ester (15 mg/kg iv, n = 7). COX-1 mRNA levels were low in time controls, and ischemic stress had no significant effect on COX-1 expression. Thus ischemic stress leads to relatively rapid, selective induction of COX-2 in cerebral arteries.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA. fdomoki@wfubmc.edu
authors.forename: F
authors.initials: F
authors.lastname: Domoki
authors.forename: R
authors.initials: R
authors.lastname: Veltkamp
authors.forename: N
authors.initials: N
authors.lastname: Thrikawala
authors.forename: G
authors.initials: G
authors.lastname: Robins
authors.forename: F
authors.initials: F
authors.lastname: Bari
authors.forename: T M
authors.initials: TM
authors.lastname: Louis
authors.forename: D W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000201:enzymology*; D013552:Swine
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases