Misawa M, Takata T
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Jpn J Pharmacol. 1988 Sep;48(1):7-13. doi: 10.1254/jjp.48.7.
Effects of platelet-activating factor (PAF) on the rat airways were investigated. Male Wistar rats were anesthetized, and PAF was inhaled into the lungs through a tracheal cannula for 5 min using an ultrasonic nebulizer. The bronchomotor response was measured with a modified Konzett-Rössler method in rats immobilized with decamethonium bromide. The inhalation of PAF caused a marked bronchoconstriction, dose-dependently, in a concentration range of 0.0001 to 0.01%. The bronchoconstrictor potency of PAF was about ten times higher than that of ACh. On the other hand, histamine inhalation gave only a slight bronchoconstriction even at the high concentration of 0.1%. The bronchomotor response to PAF was accompanied by a marked, sustained decrease in systemic blood pressure, in a dose-dependent manner. Repeated inhalations of PAF (0.001%) at an interval of 60 min resulted in a pronounced tachyphylaxis in the bronchoconstrictor response, but not in the hypotensive response. Combined inhalations of PAF with ACh or histamine did not produce a potentiation by PAF of the bronchoconstrictor responses to ACh and histamine. These findings show that PAF is a strong bronchoconstrictor agent in rats and that there is no interaction between PAF and other mediators in the acute bronchoconstrictor response.
研究了血小板活化因子(PAF)对大鼠气道的影响。将雄性Wistar大鼠麻醉后,使用超声雾化器通过气管插管将PAF吸入肺中5分钟。用改良的Konzett-Rössler方法在溴化十烃季铵固定的大鼠中测量支气管运动反应。在0.0001%至0.01%的浓度范围内,吸入PAF会引起明显的剂量依赖性支气管收缩。PAF的支气管收缩效力比乙酰胆碱(ACh)高约十倍。另一方面,即使在0.1%的高浓度下,吸入组胺也只会引起轻微的支气管收缩。对PAF的支气管运动反应伴随着全身血压明显、持续的下降,呈剂量依赖性。以60分钟的间隔重复吸入PAF(0.001%)会导致支气管收缩反应出现明显的快速耐受性,但低血压反应中不会出现。PAF与ACh或组胺联合吸入不会使PAF增强对ACh和组胺的支气管收缩反应。这些发现表明,PAF是大鼠体内一种强效的支气管收缩剂,并且在急性支气管收缩反应中PAF与其他介质之间不存在相互作用。