Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs.
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.
Leffler
C W
CW
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Thompson
C
C
Shibata
M
M
Armstead
W M
WM
Pourcyrous
M
M
Thelin
O
O
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001160:Arterioles / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology*; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D010100:Oxygen