Suppression of the cough reflex by α2-adrenergic receptor agonists in the rabbit
Suppression of the cough reflex by α2-adrenergic receptor agonists in the rabbit
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DOI：
10.1002/phy2.122
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发表时间：
2013-11-01
影响因子：
2.5
通讯作者：
Mutolo, Donatella
中科院分区：
文献类型：
--
作者：
Cinelli, Elenia;Bongianni, Fulvia;Mutolo, Donatella
α(2)-肾上腺素能受体激动剂可乐定在雾化吸入时可抑制柠檬酸引起的豚鼠咳嗽反应，但不能口服。相比之下，口服或吸入可乐定对辣椒素引起的人类咳嗽和反射性支气管收缩没有影响。此外，静脉注射可乐定已被证明可以抑制芬太尼在人体内引起的咳嗽。我们研究了α(2)-肾上腺素能受体激动剂可乐定和替扎尼定对机械和化学(柠檬酸)刺激气管支气管树引起的咳嗽反应的影响。在戊巴比妥钠麻醉的自主呼吸兔，将药物(30-50nL)微量注射到尾侧孤束核(CNTs)和尾侧腹侧呼吸群(CVRG)，并静脉注射给药。双侧CNT或cVRG内微量注射可乐定0.5 mmol/L可使咳嗽反应减弱，5 mm ol/L时可完全消除咳嗽反射。CNT内微量注射0.5 mm ol/L替扎尼定可完全抑制咳嗽反应，而cVRG内微量注射5 mm ol/L仅使咳嗽反应轻微减轻。微量注射10 mmol/L育亨宾可完全逆转可乐定和替扎尼定对咳嗽反射的抑制作用。静脉注射可乐定(80-120克/公斤)或替扎尼定(150-300克/公斤)可显著减轻或完全抑制咳嗽反应。静脉注射育亨宾(300lg/kg)可逆转上述作用。结果表明，激活兔的α(2)-肾上腺素能受体对产生咳嗽运动模式的中枢机制有很强的抑制作用，在CNTs和cVRG水平有明显的作用。
The alpha(2)-adrenergic receptor agonist clonidine has been shown to inhibit citric acid-induced cough responses in guinea pigs when administered by aerosol, but not orally. In contrast, oral or inhaled clonidine had no effect on capsaicin-induced cough and reflex bronchoconstriction in humans. In addition, intravenous administration of clonidine has been shown to depress fentanyl-induced cough in humans. We investigated the effects of the alpha(2)-adrenergic receptor agonists, clonidine and tizanidine, on cough responses induced by mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30-50 nL) into the caudal nucleus tractus solitarii (cNTS) and the caudal ventral respiratory group (cVRG) as well as administered intravenously in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections of clonidine into the cNTS or the cVRG reduced cough responses at 0.5 mmol/L and abolished the cough reflex at 5 mmol/L. Bilateral microinjections of 0.5 mmol/L tizanidine into the cNTS completely suppressed cough responses, whereas bilateral microinjections of 5 mmol/L into the cVRG only caused mild reductions in them. Depressant effects on the cough reflex of clonidine and tizanidine were completely reverted by microinjections of 10 mmol/L yohimbine. Intravenous administration of clonidine (80-120 lg/kg) or tizanidine (150-300 lg/kg) strongly reduced or completely suppressed cough responses. These effects were reverted by intravenous administration of yohimbine (300 lg/kg). The results demonstrate that activation of alpha(2)-adrenergic receptors in the rabbit exerts potent inhibitory effects on the central mechanism generating the cough motor pattern with a clear action at the level of the cNTS and the cVRG.