PMID- 11373343
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20210511
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 12
IP  - 6
DP  - 2001 Jun
TI  - Countervailing influence of tumor necrosis factor-alpha and nitric oxide in 
      endotoxemia.
PG  - 1204-1210
LID - 10.1681/ASN.V1261204 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha), a crucial mediator in sepsis, elicits 
      multiple biologic effects, including intravascular thrombosis and circulatory 
      shock. TNF-alpha exerts its biologic effects through two distinct cell surface 
      receptors, TNF-R1 and TNF-R2. The pathophysiologic interaction between TNF-alpha 
      and nitric oxide (NO) in glomerular thrombosis caused by endotoxemia in rats and 
      wild-type mice (C57BL6) as well as in knockout mice that are deficient in TNF-R1 
      (R1 -/-), TNF-R2 (R2 -/-), or both receptors (R1R2 -/-) was studied. 
      Administration of lipopolysaccharide (LPS; Escherichia coli endotoxin) resulted 
      in increased NO and TNF-alpha production but failed to induce glomerular 
      thrombosis. Concomitant administration of LPS + NG-nitro-L-arginine methyl ester 
      (L-NAME; an NO synthesis inhibitor) resulted in glomerular thrombosis in rats and 
      in wild-type mice. Intraperitoneal administration of pentoxifylline before LPS 
      inhibited TNF-alpha synthesis and prevented glomerular thrombosis in rats given 
      LPS + L-NAME. In contrast to the results observed in rats and wild-type mice, 
      administration of LPS + L-NAME did not result in glomerular thrombosis in 
      knockout mice with either single or double TNF-alpha receptor deletion. Thus, 
      during endotoxemia, (1) TNF-alpha fosters glomerular thrombosis if there is 
      deficiency of NO synthesis and (2) both TNF-alpha receptors are necessary for 
      TNF-alpha's prothrombogenic action. Clinically, these novel studies suggest that 
      in gram-negative endotoxemia, inhibition of NO synthesis and selective blockade 
      of TNF-alpha receptors may provide unique therapeutic approaches for mitigation 
      of glomerular thrombosis and restitution of vascular tone.
FAU - Jaimes, Edgar A
AU  - Jaimes EA
AD  - Nephrology and Hypertension Section, Veterans Administration Medical Center, 
      Minneapolis, Minnesota.
FAU - Castillo, Domingo Del
AU  - Castillo DD
AD  - Nephrology and Hypertension Section, Veterans Administration Medical Center, 
      Minneapolis, Minnesota.
FAU - Rutherford, Mark S
AU  - Rutherford MS
AD  - Department of Veterinary Pathobiology, University of Minnesota, Minneapolis, 
      Minnesota.
FAU - Raij, Leopoldo
AU  - Raij L
AD  - Nephrology and Hypertension Section, Veterans Administration Medical Center, 
      Minneapolis, Minnesota.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - SD6QCT3TSU (Pentoxifylline)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Endotoxemia/enzymology/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Escherichia coli
MH  - Kidney Glomerulus/*metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/*metabolism
MH  - Pentoxifylline/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thrombosis/*etiology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2001/05/25 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/05/25 10:00
PHST- 2001/05/25 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/05/25 10:00 [entrez]
AID - 12/6/1204 [pii]
AID - 10.1681/ASN.V1261204 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2001 Jun;12(6):1204-1210. doi: 10.1681/ASN.V1261204.