Effects of inhaled heparin on immunologic and nonimmunologic bronchoconstrictor responses in sheep

T. Ahmed, W. M. Abraham, J. D'Brot

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74 Scopus citations

Abstract

The glycosaminoglycan heparin has been shown to block inositol triphosphate (IP3) receptors in various tissues. Because IP3 is one of the pathways involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit airway anaphylaxis. Thus, the purpose of the present investigation was to study the effect of inhaled heparin on immunologically and nonimmunologically induced bronchoconstriction in allergic sheep. Specific lung resistance (SRL) was measured in 15 sheep allergic to Ascaris suum antigen, before and after inhalation challenge with the specific antigen, compound 48/80, histamine, and carbachol. On a different day, the animals were pretreated with inhaled heparin and airway challenges with the antigen and agonists were repeated. Antigen alone increased SRL by 367 ± 119% (mean ± SE) above baseline (p < 0.05). Inhaled heparin had no effect on baseline SRL, but attenuated antigen-induced bronchoconstriction in a dose-dependent fashion: mean SRL increased by 313 ± 87, 151 ± 69, and 24 ± 20% above baseline with 100, 300, and 1,000 U/kg of heparin, respectively. Inhaled benzyl alcohol preservative, dextran sulfate, and de-N-sulfated heparin failed to inhibit antigen-induced bronchoconstriction. The dose of heparin (1,000 U/kg) that completely blocked antigen-induced bronchoconstriction also attenuated the bronchoconstriction induced by compound 48/80 (ΔSRL = 374 ± 72 versus 35 ± 12%), but failed to block the bronchoconstrictor effects of histamine and carbachol. These data suggest that inhaled heparin prevents bronchoconstrictor responses induced by stimuli that produce immunologic and nonimmunologic mast-cell degranulation in sheep, without attenuating agonist-induced bronchoconstriction. This action of heparin may be related to modulation of mast-cell mediator release rather than inhibition of airway smooth muscle contraction.

Original languageEnglish (US)
Pages (from-to)566-570
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume145
Issue number3
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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