title: Pharmacological modulation of platelet activating factor (PAF)-induced bronchoconstriction and hypertension in anaesthetized guinea-pigs.
abstract: The effect of PAF has been examined in anaesthetized guinea-pigs. Intravenous (i.v.) administration of PAF (10 ng kg-1) did not modify the respiratory response but decreased the arterial blood pressure. A high dose of PAF (200 ng kg-1) caused marked bronchoconstriction and concomitant hypertension. The cyclooxygenase inhibitors aspirin (5 mg kg-1) and indomethacin (5 mg kg-1) and the thromboxane A2 (TXA2) receptor antagonist BM-13.177 (1 mg kg-1) failed to inhibit the peak bronchoconstrictive response but significantly inhibited the prolonged response following peak response. These inhibitors also attenuated PAF-induced hypertension. On the other hand, the lipoxygenase inhibitors phenidone (10 mg kg-1) and NDGA (5 mg kg-1) and the leukotriene (LT) receptor antagonist FPL-55712 (2 mg kg-1) affected neither bronchoconstriction nor hypertension induced by PAF. However, when aspirin was given in combination with NDGA, phenidone or FPL-55712, the peak and the following prolonged bronchoconstriction were significantly inhibited. The suppression of PAF-induced hypertension by aspirin was not further inhibited by the combination of these inhibitors. These results indicate that in anaesthetized guinea-pigs PAF-induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response). The latter may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by the generation of TXA2.
authors.affiliation: Biological and Chemical Laboratory, Nissan Chemical Co., Ltd., Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwama
authors.forename: K
authors.initials: K
authors.lastname: Shikada
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001986:Bronchial Spasm / Q000209:etiology* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D013928:Thromboxane A2; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases