Tumor necrosis factor-α induces pial arteriolar dilation in newborn pigs

Masaaki Shibata, Elena Parfenova, Samuel L. Zuckerman, Charles Leffler

Research output: Contribution to journalArticle

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Abstract

The present study in piglets was designed to examine cerebrovascular effects of tumor necrosis factor-α (TNFα) and potential mechanisms involved. Anesthetized newborn pigs with closed cranial windows implanted were used. Effects of nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L- arginine (L-NNA) and aminoguanidine, and a prostaglandin H synthase inhibitor, indomethacin, on pial arteriolar responses to TNFα were determined. In addition, cortical cerebrospinal fluid (CSF) prostanoids (PGE2 and 6-keto-PGF(1α)) and cyclic nucleotides (cAMP and cGMP) were examined as indices of local cerebral production. Diameters of pial arterioles were recorded every 5 min for 30 min following topical infusion of TNFα under the window. CSF was sampled at the end of the 30-min recordings. TNFα (10-8 and 10-7 M) caused dilation of pial arterioles and increased CSF prostanoids and cyclic nucleotides. Indomethacin blocked TNFα-induced vasodilation and the increase of prostanoids and cAMP, but not of cGMP. L- NNA and aminoguanidine blocked TNFα-induced vasodilation. Both inhibitors attenuated TNFα-induced prostanoid increase. Aminoguanidine blocked TNFα- induced increased cGMP and attenuated the increase in cAMP. These results are consistent with the hypothesis that TNFα increases cAMP via prostanoid synthesis. They also suggest that TNFα increases cGMP through nitric oxide synthesis, which, in addition, may promote production of prostanoids and, thus, cAMP.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalBrain Research Bulletin
Volume39
Issue number4
DOIs
StatePublished - Jan 1 1996

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Dilatation
Swine
Tumor Necrosis Factor-alpha
Prostaglandins
Cerebrospinal Fluid
Cyclic Nucleotides
Arterioles
Vasodilation
Indomethacin
Cyclooxygenase Inhibitors
Prostaglandins F
Prostaglandin-Endoperoxide Synthases
Dinoprostone
Nitric Oxide Synthase
Arginine
Nitric Oxide
pimagedine

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Tumor necrosis factor-α induces pial arteriolar dilation in newborn pigs. / Shibata, Masaaki; Parfenova, Elena; Zuckerman, Samuel L.; Leffler, Charles.

In: Brain Research Bulletin, Vol. 39, No. 4, 01.01.1996, p. 241-247.

Research output: Contribution to journalArticle

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