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Aerosolized and intravenously administered leukotrienes: effects on the bronchoconstrictor potency of histamine in the guinea‐pig
Author(s) -
Fennessy M.R.,
Stewart A.G.,
Thompson D.C.
Publication year - 1986
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.1476-5381.1986.tb14592.x
Subject(s) - histamine , bronchoconstriction , potency , leukotriene d4 , leukotriene c4 , leukotriene , saline , guinea pig , airway resistance , chemistry , ec50 , endocrinology , pharmacology , medicine , respiratory system , asthma , in vitro , biochemistry
1 The effects of leukotrienes C 4 and D 4 (LTC 4 and LTD 4 ), administered intravenously or by aerosol, on the bronchoconstrictor potency of intravenously administered histamine have been investigated in anaesthetized, mechanically ventilated guinea‐pigs. 2 LTC 4 (2 n m ) had no effect on either the EC 50 or the maximum contractile response to histamine on the isolated trachea of the guinea‐pig. At 10 n m , LTC 4 induced a rightward shift in the histamine concentration‐response curve without affecting the maximum response. 3 LTD 4 (0.05–0.20 nmol kg −1 , i.v.) dose‐dependently enhanced histamine (9–36 nmol kg −1 , i.v.)‐induced increases in airways resistance, whereas equibronchoconstrictor doses of LTC 4 (0.1–0.4 nmol kg −1 , i.v.), failed to enhance histamine‐induced increases in airways resistance. 4 Aerosols of LTC 4 and LTD 4 generated from solutions of 1–16 μ m and administered for 30 s, elicited concentration‐dependent bronchoconstrictions comprising decreases in dynamic compliance and increases in airways resistance. At 20 min after exposure to these aerosols, the potency of histamine (9–36 nmol kg −1 , i.v.) was significantly increased on both airways resistance and dynamic compliance. 5 The potentiation induced by LTC 4 (4 μ m , 30 s) was maintained up to 60 min after aerosol exposure whereas that induced by LTD 4 (4 μ m , 30 s) was maintained up to 40 min after aerosol exposure but was not significantly different ( P > 0.05, unpaired Student's t test) to saline‐exposed animals at 60 min. 6 LTC 4 , as has been previously reported for LTD 4 , does not enhance the histamine‐induced contraction of isolated airways smooth muscle. In contrast to LTD 4 , intravenously administered LTC 4 does not appear to enhance histamine‐induced bronchoconstriction. On the other hand, aerosols of either LTC 4 or LTD 4 potentiate histamine in vivo in a concentration‐dependent manner. These data suggest that leukotrienes may contribute to the regulation of airways reactivity to histamine in the guinea‐pig.