Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebralarteries

In the newborn, cyclooxygenase (COX)-derived products play an important rol e in the cerebrovascular dysfunction after ischemia-reperfusion (I/R). We e xamined effects of I/R on expression of COX-1 and COX-2 isoforms in large c erebral 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). Tissu es were analyzed for COX-1 and COX-2 mRNA and protein using RNase protectio n assay and immunoblot analysis, respectively. Ischemia increased COX-2 mRN A 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 consiste ntly 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 in duction of COX-2 in cerebral arteries.