Departamento de Enfermería, Universidad de Valladolid, 47005 Valladolid, Spain.
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid 47005 Spain.
Int J Mol Sci. 2020 Jul 10;21(14):4893. doi: 10.3390/ijms21144893.
The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO 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.
睡眠呼吸暂停低通气综合征（SAHS）涉及间歇性低氧期，通过使动物模型暴露于振荡 PO 模式来实验再现。在这两种情况下，慢性间歇性低氧（CIH）暴露会导致颈动脉体（CB）过度兴奋，从而增加对脑干的输入，从而导致交感神经活性亢进，随后发生高血压，而 CB 去神经支配可消除高血压。CB 在化学感受器细胞中具有多巴胺（DA）受体，作为 DA-2 自身受体发挥作用。目的是检查阻断 DA-2 受体是否可以降低 CIH 引起的 CB 过敏反应，从而最大程度地减少与 CIH 相关的影响。使用多潘立酮（DOM），一种选择性外周 DA-2 受体拮抗剂，不会穿过血脑屏障，以检查其对 CIH（30 天）暴露大鼠的影响。测量动脉压，CB 分泌活性和全身 plethysmography。在 CIH 的最后 15 天内急性或慢性给予 DOM，可逆转 CIH 引起的高血压，与 CB 去神经支配获得的类似效果。DOM 轻度降低了对照组动物的血压，并且不影响对照组或 CIH 动物的低氧通气反应。未观察到不良反应。多潘立酮（DOM）作为胃肠动力药和止吐药，可能为对标准治疗有抵抗的 SAHS 患者的高血压提供治疗机会。
