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Effect of CP-96,345, a non-peptide NK1 receptor antagonist, against substance P-, bradykinin- and allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig



Effect of CP-96,345, a non-peptide NK1 receptor antagonist, against substance P-, bradykinin- and allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig



European Journal Of Pharmacology. 231(1): 31-38



We have investigated the effect of a new non-peptide NK-1 receptor antagonist, CP-96,345, against substance P (SP)-, bradykinin (BK)- and allergen-induced airway microvascular leakage, bronchoconstriction and hypotension in anesthetized guinea pigs. Lung resistance (R-L) and mean systemic blood pressure (BP) were measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. I.v. (2 nmol/kg) and inhaled (1 mM, 45 breaths) SP, i.v. (15 nmol/kg) and inhaled (1 mM, 45 breaths) BK and aerosolized allergen (5 mg/ml of ovalbumin, 30 breaths) induced a significant increase in R-L and leakage of dye at all airway levels, and decreased BP significantly except for inhaled BK. CP-96,345 (2 mg/kg i.v.) abolished the dye extravasation induced by both SP. CP-96,345 partly inhibited the responses induced by both BK but not by allergen. CP-96,345 markedly inhibited the increase in R-L and fall in BP induced by SP but not by BK or allergen. NK-1 receptor-mediated mechanisms may contribute to SP- and BK-induced airway microvascular leakage and SP-induced bronchoconstriction and hypotension. These mechanisms are not important in the acute airway responses induced by inhaled allergen.

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Accession: 008518673

Download citation: RISBibTeXText

PMID: 7680318

DOI: 10.1016/0014-2999(93)90680-g


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