Tumor necrosis factor-α-induced dilatation of cerebral arterioles

被引:59
作者
Brian, JE [1 ]
Faraci, FM
机构
[1] Univ Iowa, Coll Med, Dept Anesthesia 6 JCP, Ctr Cardiovasc, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Dept Internal Med & Pharmacol, Iowa City, IA 52242 USA
关键词
cerebral arteries; dexamethasone; nitric oxide synthase; tumor necrosis factor; vasodilation;
D O I
10.1161/01.STR.29.2.509
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
dBackground and Purpose-In brain, several cell types produce tumor necrosis factor-alpha (TNF alpha) after injury or exposure to endotoxin. TNF alpha alone or in combination with endotoxin or other cytokines can cause expression of inducible nitric oxide (NO) synthase. We have previously demonstrated that endotoxin caused NO-dependent dilatation of cerebral arterioles in vivo. In the present study we examined the hypothesis that TNF alpha causes NO-mediated dilatation of cerebral arterioles in vivo. Methods-Cranial windows were implanted in anesthetized rats and used to measure the diameter of cerebral arterioles. Windows were flushed every 30 minutes for 4 hows with artificial cerebrospinal fluid (aCSF) (n=6); aCSF with TNF alpha (100 ng/mL; n=10); aCSF with TNF alpha and aminoguanidine (0.3 mmol/L; n=5), an inhibitor of inducible NO synthase; or aCSF with TNF alpha and dexamethasone (1 mu mol/L; n=6), which attenuates expression of inducible NO synthase. In some animals, brain from beneath the cranial window was examined by immunocytochemistry for inducible NO synthase expression. Results-Application of TNF alpha caused marked, progressive dilatation of cerebral arterioles, with a maximum increase in diameter of 46+/-9% (mean+/-SEM) at 4 hours. Coapplication of either aminoguanidine or dexamethasone with TNF alpha prevented dilatation of cerebral arterioles compared with TNF alpha alone (4+/-2% and 1+/-1% dilatation at 4 hours, respectively; P<.05). Dexamethasone did not inhibit dilatation of cerebral arterioles in response to adenosine diphosphate. However, 2 hours of aminoguanidine treatment produced moderate inhibition of adenosine diphosphate-induced dilatation of cerebral arterioles. After treatment with TNF alpha, immunocytochemistry for inducible NO synthase demonstrated expression in perivascular and arachnoid cells but not brain cells. There was no detectable expression of inducible NO synthase after treatment with aCSF. Conclusions-The present study indicates that TNF alpha causes cerebral vasodilatation and expression of inducible NO synthase in perivascular and arachnoid cells. Inhibition of TNF alpha-induced dilatation by aminoguanidine and dexamethasone suggests that the vasodilatation was due predominantly to expression of inducible NO synthase. These findings support the concept that cerebral vasodilatation that occurs during pathophysiological conditions associated with increased TNF alpha production in brain is mediated by expression of inducible NO synthase.
引用
收藏
页码:509 / 515
页数:7
相关论文
共 49 条
[31]   THE BENEFICIAL-EFFECTS OF EARLY DEXAMETHASONE ADMINISTRATION IN INFANTS AND CHILDREN WITH BACTERIAL-MENINGITIS [J].
ODIO, CM ;
FAINGEZICHT, I ;
PARIS, M ;
NASSAR, M ;
BALTODANO, A ;
ROGERS, J ;
SAEZLLORENS, X ;
OLSEN, KD ;
MCCRACKEN, GH .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (22) :1525-1531
[32]   MICROVASCULAR CHANGES DURING THE EARLY PHASE OF EXPERIMENTAL BACTERIAL-MENINGITIS [J].
PFISTER, HW ;
KOEDEL, U ;
HABERL, RL ;
DIRNAGL, U ;
FEIDEN, W ;
RUCKDESCHEL, G ;
EINHAUPL, KM .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1990, 10 (06) :914-922
[33]   RAPID INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE CEREBROSPINAL-FLUID AFTER INTRACEREBROVENTRICULAR INJECTION OF LIPOPOLYSACCHARIDE REVEALED BY A SENSITIVE CAPTURE IMMUNO-PCB ASSAY [J].
SANNA, PP ;
WEISS, F ;
SAMSON, ME ;
BLOOM, FE ;
PICH, EM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (01) :272-275
[34]   THE ROLE OF CYTOKINES IN THE GENERATION OF INFLAMMATION AND TISSUE-DAMAGE IN EXPERIMENTAL GRAM-POSITIVE MENINGITIS [J].
SAUKKONEN, K ;
SANDE, S ;
CIOFFE, C ;
WOLPE, S ;
SHERRY, B ;
CERAMI, A ;
TUOMANEN, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (02) :439-448
[35]   ROLE OF TRANSCRIPTIONAL ACTIVATION OF I-KAPPA-B-ALPHA IN MEDIATION OF IMMUNOSUPPRESSION BY GLUCOCORTICOIDS [J].
SCHEINMAN, RI ;
COGSWELL, PC ;
LOFQUIST, AK ;
BALDWIN, AS .
SCIENCE, 1995, 270 (5234) :283-286
[36]   Tumor necrosis factor-alpha induces pial arteriolar dilation in newborn pigs [J].
Shibata, M ;
Parfenova, H ;
Zuckerman, SL ;
Leffler, CW .
BRAIN RESEARCH BULLETIN, 1996, 39 (04) :241-247
[37]   CLOSED-HEAD INJURY TRIGGERS EARLY PRODUCTION OF TNF-ALPHA AND IL-6 BY BRAIN-TISSUE [J].
SHOHAMI, E ;
NOVIKOV, M ;
BASS, R ;
YAMIN, A ;
GALLILY, R .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1994, 14 (04) :615-619
[38]   CYTOKINES REGULATE L-ARGININE-DEPENDENT CYCLIC-GMP PRODUCTION IN RAT GLIAL-CELLS [J].
SIMMONS, ML ;
MURPHY, S .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1993, 5 (07) :825-831
[39]   ROLES FOR PROTEIN-KINASES IN THE INDUCTION OF NITRIC-OXIDE SYNTHASE IN ASTROCYTES [J].
SIMMONS, ML ;
MURPHY, S .
GLIA, 1994, 11 (03) :227-234
[40]   INDUCTION OF NITRIC-OXIDE SYNTHASE IN GLIAL-CELLS [J].
SIMMONS, ML ;
MURPHY, S .
JOURNAL OF NEUROCHEMISTRY, 1992, 59 (03) :897-905