PMID- 1741548
OWN - NLM
STAT- MEDLINE
DCOM- 19920109
LR  - 20071114
IS  - 0003-0805 (Print)
IS  - 0003-0805 (Linking)
VI  - 144
IP  - 6
DP  - 1991 Dec
TI  - Role of platelet-activating factor in mediating tumor necrosis factor 
      alpha-induced pulmonary vasoconstriction and plasma-lymph protein transport.
PG  - 1337-41
AB  - We assessed the role of platelet-activating factor (PAF) in mediating the 
      pulmonary hemodynamic and lymph flow responses to tumor necrosis factor-alpha 
      (TNF alpha). The effects of the PAF receptor antagonist WEB 2086 on TNF 
      alpha-induced pulmonary vasoconstriction and increased pulmonary transvascular 
      plasma-lymph protein transport were examined. Control (n = 7) and 
      WEB-2086-pretreated (n = 7) sheep prepared with chronic lung lymph fistulas were 
      challenged with recombinant human TNF alpha (12 micrograms/kg over 0.5 h). Ex 
      vivo challenge of platelet-rich plasma (PRP) with 10(-8) M PAF resulted in 
      aggregation of platelets from control TNF-challenged sheep, but not of platelets 
      from WEB-treated sheep similarly challenged with TNF. The control 
      TNF-alpha-challenged sheep developed hemoconcentration, leukopenia, and 
      neutropenia. TNF alpha resulted in increases in pulmonary arterial pressure (Ppa) 
      and pulmonary vascular resistance (PVR) within 15 min, and the values were 
      sustained for the 5-h experiment duration. Pulmonary lymph flow (Qlym) and 
      pulmonary transvascular protein clearance rate (Qlym x lymph-to-plasma protein 
      concentration) were increased within 30 min and remained elevated for 5 h. The 
      WEB-2086-treated sheep developed similar leukopenia and neutropenia after TNF 
      alpha challenge, but the initial increases in Ppa and PVR were significantly 
      reduced (p less than 0.05). However, WEB 2086 did not prevent the threefold 
      increases in Qlym and transvascular protein clearance induced with TNF 
      alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Horvath, C J
AU  - Horvath CJ
AD  - Department of Physiology and Cell Biology, Albany Medical College of Union 
      University, New York 12208.
FAU - Kaplan, J E
AU  - Kaplan JE
FAU - Malik, A B
AU  - Malik AB
LA  - eng
GR  - HL 27016/HL/NHLBI NIH HHS/United States
GR  - HL-32418/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am Rev Respir Dis
JT  - The American review of respiratory disease
JID - 0370523
RN  - 0 (Azepines)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Triazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 105219-56-5 (WEB 2086)
SB  - IM
MH  - Animals
MH  - Azepines/pharmacology
MH  - Capillary Permeability/physiology
MH  - Lymphatic System/*physiology
MH  - Male
MH  - Platelet Activating Factor/antagonists & inhibitors/*physiology
MH  - Pulmonary Veins/*physiology
MH  - Sheep
MH  - Triazoles/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vasoconstriction/*physiology
EDAT- 1991/12/01 00:00
MHDA- 1991/12/01 00:01
CRDT- 1991/12/01 00:00
PHST- 1991/12/01 00:00 [pubmed]
PHST- 1991/12/01 00:01 [medline]
PHST- 1991/12/01 00:00 [entrez]
AID - 10.1164/ajrccm/144.6.1337 [doi]
PST - ppublish
SO  - Am Rev Respir Dis. 1991 Dec;144(6):1337-41. doi: 10.1164/ajrccm/144.6.1337.