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Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits
Author(s) -
Sasaki Masahiro,
Herd Caroline M.,
Page Clive P.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13778.x
Subject(s) - heparinoid , heparin , bronchoconstriction , bronchoalveolar lavage , histamine , pharmacology , platelet activating factor , chemistry , immunology , medicine , lung , asthma
1 We have investigated the effect of an unfractionated heparin preparation, a low‐molecular weight heparinoid (Org 10172) and the polyanionic molecule polyglutamic acid against PAF‐induced airway hyperresponsiveness and pulmonary cell infiltration in neonatally immunized rabbits in vivo . 2 Exposure of neonatally immunized rabbits to aerosolized platelet activating factor (PAF) (80 μg ml −1 for 60 min) elicited an increase in airway responsiveness to inhaled histamine 24 h and 72 h following challenge which was associated with an infiltration of inflammatory cells into the airways, as assessed by bronchoalveolar lavage (BAL). 3 A significant increase in the total numbers of cells recovered from BAL fluid was associated with significantly increased cell numbers of neutrophils, eosinophils and mononuclear cells 24 h following PAF exposure. The numbers of eosinophils and neutrophils in the airways remained elevated 72 h after challenge. 4 The intravenous administation of an unfractionated preparation of heparin (100 units kg −1 ) or Org 10172 (100 μg kg −1 ) 30 min prior to PAF exposure significantly inhibited the airway hyperresponsiveness induced by PAF, 24 h and 72 h following challenge. PAF‐induced hyperresponsiveness was not significantly affected by prior intravenous administration of polyglutamic acid (100 μg kg −1 ). 5 The intravenous administration of unfractionated heparin (100 units kg −1 ), Org 10172 (100 μg kg −1 ) or polyglutamic acid (100 μg kg −1 ) 30 min prior to PAF exposure significantly inhibited the expected increase in total cell infiltration. 6 This study shows that unfractionated heparin and a low‐molecular weight heparinoid, Org 10172, are capable of inhibiting both the airway hyperresponsiveness and pulmonary cell infiltration induced by PAF in the rabbit.