In newborn pigs, vasodilation in response to
hypercapnia is dependent on
prostaglandin (PG) H synthase. We investigated the contribution of activated
oxygen by-products to
hypercapnia-induced
PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated
oxygen species were generated on the cerebral surface using
xanthine oxidase and
hypoxanthine.
Catalase, H2O2, and
iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of
superoxide anion and
hydroxyl radical. All the activated
oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated
oxygen species was largely reversible with only the
hydroxyl radical encouraging combination of
xanthine oxidase,
hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular
superoxide anion radical scavenger,
superoxide dismutase (SOD), the intracellular
superoxide anion radical scavenger,
Tiron, the H2O2 scavenger,
catalase, nor
hydroxyl radical scavengers,
dimethyl sulfoxide (
DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to
hypercapnia. Furthermore, the increase in cerebral
prostanoid synthesis in response to
hypercapnia was not affected by pretreatment with SOD,
Tiron,
catalase,
DMSO, or MPG. We conclude that the progressively reduced forms of
oxygen that would be produced during
PGH synthase metabolism of
arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated
oxygen species are not responsible for the vasodilation to
hypercapnia in the newborn pig, suggesting that
eicosanoids cause the dilation.