title: Tumor necrosis factor-alpha induces pial arteriolar dilation in newborn pigs.
abstract: The present study in piglets was designed to examine cerebrovascular effects of tumor necrosis factor-alpha (TNF alpha) and potential mechanisms involved. Anesthetized new-born pigs with closed cranial windows implanted were used. Effects of nitric oxide synthase (NOS) inhibitors, NG-nitro-L-arginine (L-NNA) and aminoguanidine, and a prostaglandin H synthase inhibitor, indomethacin, on pial arteriolar responses to TNF alpha were determined. In addition, cortical cerebrospinal fluid (CSF) prostanoids (PGE2 and 6-keto-PGF1 alpha) 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 TNF alpha under the window. CSF was sampled at the end of the 30-min recordings. TNF alpha (10(-8) and 10(-7) M) caused dilation of pial arterioles and increased CSF prostanoids and cyclic nucleotides. Indo-methacin blocked TNF alpha-induced vasodilation and the increase of prostanoids and cAMP, but not of cGMP. L-NNA and amino-guanidine blocked TNF alpha-induced vasodilation. Both inhibitors attenuated TNF alpha-induced prostanoid increase. Aminoguanidine blocked TNF alpha-induced increased cGMP and attenuated the increase in cAMP. These results are consistent with the hypothesis that TNF alpha increases cAMP via prostanoid synthesis. They also suggest that TNF alpha increases cGMP through nitric oxide synthesis, which, in addition, may promote production of prostanoids and, thus, cAMP.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: S L
authors.initials: SL
authors.lastname: Zuckerman
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D015232:Dinoprostone