Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs

Charles Leffler, R. Mirro, C. Thompson, M. Shibata, W. M. Armstead, Massroor Pourcyrous, O. Thelin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number2 30-2
StatePublished - Jan 1 1991

Fingerprint

Hypercapnia
Vasodilation
Superoxides
Swine
Arterioles
Oxygen
Glycine
Dilatation
Prostaglandin-Endoperoxide Synthases
Arteries
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Hydroxyl Radical
Catalase
Xanthine Oxidase
Dimethyl Sulfoxide
Superoxide Dismutase
Eicosanoids
Arachidonic Acid
Prostaglandins
Iron

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs. / Leffler, Charles; Mirro, R.; Thompson, C.; Shibata, M.; Armstead, W. M.; Pourcyrous, Massroor; Thelin, O.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 261, No. 2 30-2, 01.01.1991.

Research output: Contribution to journalArticle

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N2 - 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.

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