Increased airways responsiveness to histamine induced by platelet activating factor in the guinea-pig: possible role of lipoxygenase metabolites

Abstract

In anaesthetized guinea-pigs pretreated with propranolol (1 mg/kg, i.v.), platelet activating factor (Paf, 0.02 micrograms/kg, i.v.) caused an acute increase in airways response to histamine (0.5-3.0 micrograms/kg, i.v.) measured as intratracheal pressure. Treatment with the cyclooxygenase inhibitors, aspirin (10 mg/kg, i.v.) or indomethacin (5 mg/kg, i.v.), enhanced the magnitude and duration of this effect but a combined lipoxygenase/cyclooxygenase inhibitor, BW 755C (20 mg/kg, i.v.), prevented the increase in responsiveness. In aspirin treated animals, a putative lipoxygenase inhibitor NDGA (10 mg/kg, i.v.). or atropine methyl nitrate (1 mg/kg, i.v.) or bilateral vagotomy reduced the magnitude of Paf-induced increased histamine responses but did not prevent the effect. Bronchoconstriction induced by Paf was variably influenced by the drug treatments. These data suggest that Paf causes an acute increase in airways responsiveness to histamine in the guinea-pig through a mechanism that may, in part, be dependant on the release of lipoxygenase metabolites.

Platelet‐activating factor (PAF) plays an important role in the immediate asthmatic response in guinea‐pig by augmenting the response to histamine

“…These results suggest that PAF induces a nonspecific airway hyperreactivity in nonsensitized guinea-pigs. Anderson et al (1988) reported that similar airway hyperreactivity to histamine was induced by 20ngkg-' of PAF in guinea-pigs. Our data were correlated with the potentiation rate at this dose, but we showed that larger doses of PAF provoked more marked increases in ITP in response to spasmogens.…”

Effects of NZ-107 on Bronchoconstriction in Guinea Pigs

“…Metyrapone has been recognized as an lip-hydroxylase inhibitor [16]. The ad ministration of metyrapone induced a reduction in plasma cortisol levels in guinea pigs [17] and dogs [8]. These are the reasons why we used metyrapone.…”

“…Anderson et al [8] suggested that the release of 5-lipoxygenase metabolites is involved in the PAF-in duced acute airway hyperreactivity. Sikada et al [25] re ported that NZ-107 inhibited the antigen-induced slow re acting substance of anaphylaxis (SRS-A) released from guinea pig lung fragments.…”

Interference of WEB 2086 and BN 52021 with Paf‐induced effects on guinea‐pig trachea

“…Paf-acether (Paf, formerly platelet-activating factor; Benveniste et al, 1972), identified as being 1-0-hexa/ octadecyl-2-acetyl-sn-3-glycero-phosphocholine, is a potent mediator of inflammation, which induces bronchoconstriction and airway hyperreactivity in several animal species including man (Chung et al, 1986;Cuss et al, 1986;Anderson et al, 1988). However, in vitro, this phosphoetherlipid does not contract bronchial and tracheal preparations from different species (Cerrina et al, 1983;Stimler & O'Flaherty, 1983) and paradoxically relaxes resting guinea-pig tracheal preparations (Prancan et al, 1982).…”