Hyperreflexia of the peripheral chemoreceptors is a potential contributor of apnoeas of prematurity (AoP). Recently, it was shown that elevated P2X3 receptor expression was associated with elevated carotid body afferent sensitivity. Therefore, we tested whether P2X3 receptor antagonism would reduce AoP known to occur in newborn rats. Unrestrained whole-body plethysmography was used to record breathing and from this the frequency of apnoeas at baseline and following administration of either a P2X3 receptor antagonist - AF-454 (5 mg/kg or 10 mg/kg s.c.) or vehicle was derived. In a separate group, we tested the effects of AF-454 (10 mg/kg) on the hypoxic ventilatory response (10 % FiO2). Ten but not 5 mg/kg AF-454 reduced the frequency of AoP and improved breathing regularity significantly compared to vehicle. Neither AF-454 (both 5 and 10 mg/kg) nor vehicle affected baseline respiration. However, P2X3 receptor antagonism (10 mg/kg) powerfully blunted hypoxic ventilatory response to 10 % FiO2. These data suggest that P2X3 receptors contribute to AoP and the hypoxic ventilatory response in newborn rats but play no role in the drive to breathe at rest.

中文翻译：

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P2X3 受体拮抗作用可减少新生大鼠呼吸暂停的发生。


外周化学感受器反射亢进是早产儿呼吸暂停 (AoP) 的潜在原因。最近，研究表明 P2X3 受体表达升高与颈动脉体传入敏感性升高相关。因此，我们测试了 P2X3 受体拮抗剂是否会减少新生大鼠中已知发生的 AoP。使用不受限制的全身体积描记法记录呼吸，并由此导出基线时和施用P2X3受体拮抗剂-AF-454(5mg/kg或10mg/kg sc)或赋形剂后的呼吸暂停频率。在另一组中，我们测试了 AF-454 (10 mg/kg) 对缺氧通气反应 (10% FiO2) 的影响。与载体相比，10 mg/kg 但不是 5 mg/kg 的 AF-454 显着降低了 AoP 频率并改善了呼吸规律。 AF-454（5 和 10 mg/kg）和载体均不影响基线呼吸。然而，P2X3 受体拮抗剂 (10 mg/kg) 会强烈减弱对 10% FiO2 的缺氧通气反应。这些数据表明，P2X3 受体有助于新生大鼠的 AoP 和缺氧通气反应，但在休息时呼吸驱动中不起任何作用。