Induction of cyclooxygenase-2 following anoxic stress in piglet cerebral arteries.
OBJECTIVE
Ischemic stress causes damage to cerebrovascular endothelium and alters arteriolar responses to prostanoid-dependent stimuli. However, effects of ischemic stress on cyclooxygenase (COX) levels in endothelium are unclear. We examined the effect of ischemia and reperfusion and asphyxia and reventilation on production of COX isoforms in cerebral vascular endothelium.


METHODS
Neonatal pigs were exposed to global ischemia (n = 4) or asphyxia (n = 3) for 5-10 min. Following 2-6 h of recovery, the animals were killed, and the cerebral arteries and arterioles were removed. Cerebral arteries and arterioles were also removed from untreated control animals (n = 1) and from time control animals (n = 3). Cerebral vessels were fixed in 4% formalin and paraffin embedded, and constitutive and inducible COX (COX-1 and COX-2, respectively) levels were assessed using indirect immunofluorescence.


RESULTS
Hemotoxylin and eosin staining indicated that anoxic stress leads to enlargement of endothelial cells. Immunofluorescence for COX-1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress. Similarly, cerebral vessels from control animals showed little immunostaining for COX-2. In contrast, immunofluorescence for COX-2 was greatly increased in cerebral arteries and arterioles from animals exposed to asphyxia or ischemia.


CONCLUSIONS
We concluded that anoxic stress increases COX-2 but not COX-1 levels in cerebral endothelium.
Busija
D W
DW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083, USA.
Thore
C
C
Beasley
T
T
Bari
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D002545:Brain Ischemia / Q000201:enzymology*; D002536:Cerebral Arteries / Q000201:enzymology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000201:enzymology*; D004790:Enzyme Induction; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D002534:Hypoxia, Brain / Q000201:enzymology*; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D015427:Reperfusion Injury; D013552:Swine
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases