The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients' resistant to standard treatments.

译文

:睡眠呼吸暂停低通气综合症(SAHS)涉及间歇性缺氧,通过将动物模型暴露于振荡的PO2模式进行实验性重现。在这两种情况下,慢性间歇性缺氧(CIH)暴露都会导致颈动脉体(CB)过度活化,从而增加对脑干的输入,这会引起交感神经亢进,随后是由于CB去神经支配而导致的高血压。 CB在化学感受器细胞中具有多巴胺(DA)受体作为DA-2自身受体。目的是检查阻断DA-2受体是否可以降低CIH产生的CB超敏反应,从而最大程度地减少与CIH相关的影响。多潘立酮(DOM)是一种选择性外周DA-2受体拮抗剂,它不穿越血脑屏障,用于检查其对暴露于CIH(30天)的大鼠的作用。测量动脉压,CB分泌活性和全身体积描记法。在CIH的最后15天内,急性或长期给药的DOM逆转了CIH产生的高血压,其作用与CB失神经获得的类似。 DOM在对照动物中略微降低了血压,并且在对照或CIH动物中不影响低氧通气反应。没有观察到不良反应。 DOM被用作胃肠动力药和止吐药,可能是SAHS患者对标准疗法产生抗药性的高血压治疗机会。

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