Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation.
The effect of platelet-activating factor (acetyl glyceryl ether phosphorylcholine; PAF), a potent inflammatory mediator, on airway responsiveness was studied. In six dogs airway responsiveness was determined by measuring the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance (RL) by 5 cm H2O X L-1 X s, before and after inhalation of PAF (1 mg). PAF caused a 2.3-fold increase in RL (P less than .001) that lasted approximately 30 min. Airway hyperresponsiveness was maximal at 3 hr (mean 3.7-fold increase, P less than .001), persisted at 6 hr (P less than .005) and disappeared by 24 hr. Inhalation of 0.9% NaCl had no effect on RL or on responsiveness. PAF caused an 8-fold increase in neutrophil recovery in bronchoalveolar lavage fluid at 3 hr. OKY-046, a thromboxane synthetase inhibitor, inhibited PAF-induced bronchoconstriction and hyperresponsiveness but did not alter the increase in neutrophil recovery. We tested the specificity of the effect of OKY-046 on the release of cyclooxygenase products from canine neutrophils in vitro; OKY-046 suppressed PAF-induced generation of thromboxane and caused a small increase in prostaglandin F2 alpha release. The studies suggest that the airway hyperresponsiveness induced by PAF may depend on thromboxane generation.
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D008689:Methacrylates / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects*; D013931:Thromboxanes / Q000096:biosynthesis*
D008689:Methacrylates; D010972:Platelet Activating Factor; D013931:Thromboxanes; D007975:Leukotriene B4; C034364:ozagrel