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Paper| Volume 40, ISSUE 6, P793-805, December 15, 1985

Influence of the thromboxane antagonist BM 13.177 on the irrachidonic acid-induced increase in pulmonary vascular resistance and permeability in rabbit lungs

  • W. Seeger
    Affiliations
    Clinical Phathophysiology and Experimental Medicine / Department of Internal Medicine; Department of Clinical Chemistry and Pathobiochemistry; Lustus-Liebig-University; Klinikstraβe 36, D-63 Gieβen, FRG
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  • Ch. Ernst
    Affiliations
    Clinical Phathophysiology and Experimental Medicine / Department of Internal Medicine; Department of Clinical Chemistry and Pathobiochemistry; Lustus-Liebig-University; Klinikstraβe 36, D-63 Gieβen, FRG
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  • D. Walmrath
    Affiliations
    Clinical Phathophysiology and Experimental Medicine / Department of Internal Medicine; Department of Clinical Chemistry and Pathobiochemistry; Lustus-Liebig-University; Klinikstraβe 36, D-63 Gieβen, FRG
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  • H. Neuhof
    Affiliations
    Clinical Phathophysiology and Experimental Medicine / Department of Internal Medicine; Department of Clinical Chemistry and Pathobiochemistry; Lustus-Liebig-University; Klinikstraβe 36, D-63 Gieβen, FRG
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  • L. Roka
    Affiliations
    Clinical Phathophysiology and Experimental Medicine / Department of Internal Medicine; Department of Clinical Chemistry and Pathobiochemistry; Lustus-Liebig-University; Klinikstraβe 36, D-63 Gieβen, FRG
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DOI:https://doi.org/10.1016/0049-3848(85)90316-0
Influence of the thromboxane antagonist BM 13.177 on the irrachidonic acid-induced increase in pulmonary vascular resistance and permeability in rabbit lungs
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      Abstract

      In blood-free perfused isolated rabbit lungs increased availability of free arachidonic acid (AA), whether exogenously applied or released from the endogenous membrane phospholipid pool after different stimuli, causes an acute pulmonary artery pressor response and an increase in vascular permeability. Previous experiments suggested that the vasoconstriction is caused primarily by the cyclooxygenase product thromboxane (Tx) A2, whereas an increase in the capillary filtration coefficient must be ascribed to non-cyclooxygenase produts of AA. The influence of BM 13.177, a non-prostanoic antagonist of TxA2− and endoperoxide-effects in platelets, on the AA-induced vascular effects in isolated rabbit lungs was investigated. BM 13.177 dose-dependently inhibited the pressor responses evoked by repetitive direct application of AA (IC50 ∼ 10−6 M) or by repetitive stimulation of endogenous AA-release with the calcium ionophore A 23187 (IC50 ∼ 10−7M), with maximum reduction of the pressor responses to < 15 %. The generation of TxA2 and of prostaglandin (PG)I2 evoked by these stimuli was, however, not altered. At a concentration of 10−5 M BM 13.177 did not influence the capillary filtration coefficient, measured during venous pressure challenge, under baseline conditions and after stimulation with AA in presence of indomethacin. Conclusion: βM 13.177 acts as TxA2/endoperoxide antagonist with dose-dependent inhibition of AA-induced vasoconstriction in the pulmonary vascular bed.

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      Article info

      Publication history

      Accepted: September 10, 1985
      Received: July 2, 1985

      Identification

      DOI: https://doi.org/10.1016/0049-3848(85)90316-0

      Copyright

      © 1985 Published by Elsevier Inc.

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