Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

1662407

Reference Type

Journal Article

Title

Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension

Author(s)

Xie, J; Joseph, KO; Bagby, GJ; Giles, TD; Greenberg, SS

Year

1997

Is Peer Reviewed?

Yes

Journal

American Journal of Physiology
ISSN: 0002-9513
EISSN: 2163-5773

Report Number

BIOSIS/97/26447

Volume

273

Issue

1 Pt 2

Page Numbers

H164-H174

Language

English

PMID

9249487

Web of Science Id

WOS:A1997XK67900020

URL

https://www.physiology.org/doi/10.1152/ajpheart.1997.273.1.H164
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Abstract

We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet-activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH) in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and increased plasma concentrations of TNF-alpha and nitrate and nitrite anions (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN. Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.) abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore, 1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF-alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF-alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80 micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2) endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and PAF mediates LPS-induced APH.

Keywords

inducible nitric oxide synthase messenger ribonucleic acid; platelet-activating factor; neutrophils; mesenteric artery; sepsis