Pazhoohan Saeed, Aref Ehsan, Zare Leila, Dehghan Samaneh, Javan Mohammad, Hajizadeh Sohrab, Raoufy Mohammad Reza
Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran J Basic Med Sci. 2020 Dec;23(12):1584-1589. doi: 10.22038/ijbms.2020.46258.10683.
The modulatory effect of deep inspiration (DI) on airway constriction is impaired in asthma. However, mechanisms underlying this impairment are not clear. Since there is evidence indicating that Rho-kinase activation mediates force maintenance under oscillatory strain, we investigated the impact of Rho-kinase inhibition on the bronchodilatory effect of DI in ovalbumin (OVA) sensitized guinea pigs.
forty-eight male Dunkin Hartley guinea pigs were divided into 8 groups including saline/ constant, saline/DI, OVA/constant, OVA/DI, Rho-I/OVA/constant, Rho-I/OVA/DI, OVA-Rho-I/MCh/constant, and OVA-Rho-I/MCh/DI. Animals were subjected to 12 inhalations of OVA or saline aerosol. Guinea pigs in Rho-I/OVA/constant or DI groups were treated with the Rho-kinase inhibitor (Rho-I) (Y-27632, 1 mM aerosols) prior to the last 8 allergen inhalations and OVA-Rho-I/MCh/constant or DI groups received Y-27632 at the end of allergen sensitization protocol before methacholine challenge. The bronchodilatory effect of DI in guinea pigs that were exposed to methacholine was assessed by using an animal ventilator. The bronchodilatory effect was assessed using several parameters: the airway pressure maintenance, airway pressure recovery, and decline of airway pressure.
Results indicated that application of Y-27632 prior to methacholine challenge reduces the airway smooth muscle ability to maintain pressure and also causes further decline in airway pressure in OVA-sensitized animals undergone DI. However, the inhibition of Rho-kinase before OVA inhalations had minimal effect.
We propose that alteration of Rho-kinase signaling pathway may be one of the mechanisms underlying the impairment of DI-induced bronchodilation in OVA-sensitized guinea pigs.
深吸气（DI）对气道收缩的调节作用在哮喘中受损。然而，这种损伤的潜在机制尚不清楚。由于有证据表明Rho激酶激活介导振荡应变下的力量维持，我们研究了Rho激酶抑制对卵清蛋白（OVA）致敏豚鼠DI舒张支气管作用的影响。
48只雄性Dunkin Hartley豚鼠分为8组，包括生理盐水/持续、生理盐水/DI、OVA/持续、OVA/DI、Rho-I/OVA/持续、Rho-I/OVA/DI、OVA-Rho-I/乙酰甲胆碱/持续和OVA-Rho-I/乙酰甲胆碱/DI。动物接受12次OVA或生理盐水气雾剂吸入。Rho-I/OVA/持续或DI组的豚鼠在最后8次变应原吸入前用Rho激酶抑制剂（Rho-I）（Y-27632，1 mM气雾剂）治疗，OVA-Rho-I/乙酰甲胆碱/持续或DI组在变应原致敏方案结束后、乙酰甲胆碱激发前接受Y-27632治疗。使用动物呼吸机评估DI对暴露于乙酰甲胆碱的豚鼠的舒张支气管作用。使用几个参数评估舒张支气管作用：气道压力维持、气道压力恢复和气道压力下降。
结果表明，在乙酰甲胆碱激发前应用Y-27632会降低气道平滑肌维持压力的能力，并导致接受DI的OVA致敏动物气道压力进一步下降。然而，在OVA吸入前抑制Rho激酶的作用最小。
我们认为Rho激酶信号通路的改变可能是OVA致敏豚鼠DI诱导的支气管舒张受损的潜在机制之一。
