Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea.
Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea.
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DOI：
10.1113/ep087006
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发表时间：
2018-07
影响因子：
2.7
通讯作者：
Dopp JM
中科院分区：
文献类型：
--
作者：
Morgan BJ;Teodorescu M;Pegelow DF;Jackson ER;Schneider DL;Plante DT;Gapinski JP;Hetzel SJ;Dopp JM
阻断血管紧张素Ⅱ 1型受体（AT 1 R）可减弱慢性间歇性低氧（CIH）大鼠化学感受性反射敏感化。AT 1 R阻断和黄嘌呤氧化酶抑制均能改善CIH诱导的内皮功能障碍。我们假设氯沙坦和别嘌呤醇治疗阻塞性睡眠呼吸暂停（OSA）患者可降低化学反射敏感性，改善缺氧性血管舒张。86例呼吸暂停-低通气指数≥25次/hr且无其他心血管、肺、肾或代谢疾病的高血压患者被随机分配接受别嘌呤醇、氯沙坦或安慰剂治疗6周。其他药物和/或持续气道正压通气（CPAP）治疗保持不变。治疗前后在清醒状态下进行化学感受性反射敏感性和低氧性血管舒张试验。在正常呼吸和吸入氧分压的分级降低过程中，测量通气（呼吸速度描记法）、肌肉交感神经活动（显微神经描记法）、心率（心电图）、动脉血氧饱和度（脉搏血氧饱和度）、血压（血压计）、前臂血流量（静脉闭塞体积描记法）和脑血流速度（经颅多普勒超声）。氯沙坦和别嘌呤醇降低正常呼吸和急性缺氧时的动脉压。这两种药物都没有改变急性缺氧时交感神经、交感神经或心血管反应的斜率。我们的结论是，氯沙坦和别嘌呤醇是实现高血压OSA患者的血压控制，即使是那些谁是充分的CPAP治疗的可行的药物。
Chemoreflex sensitization produced by chronic intermittent hypoxia (CIH) in rats is attenuated by angiotensin II type 1 receptor (AT1R) blockade. AT1R blockade and xanthine oxidase inhibition both ameliorate CIH-induced endothelial dysfunction. We hypothesized treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilation in patients with obstructive sleep apnoea (OSA). Eighty-six hypertensive patients with apnoea-hypopnoea index ≥25 events/hr and no other cardiovascular, pulmonary, renal, or metabolic disease were randomly assigned to receive allopurinol, losartan, or placebo for 6 weeks. Treatment with other medications and/or continuous positive airway pressure (CPAP) remained unchanged. Tests of chemoreflex sensitivity and hypoxic vasodilation were performed during wakefulness before and after treatment. Ventilation (pneumotachography), muscle sympathetic nerve activity (microneurography), heart rate (electrocardiography), arterial oxygen saturation (pulse oximetry), blood pressure (sphygmomanometry), forearm blood flow (venous occlusion plethysmography), and cerebral flow velocity (transcranial Doppler ultrasound) were measured during eupneic breathing and graded reductions in inspired O2 tension. Losartan and allopurinol lowered arterial pressure measured during eupneic breathing and exposure to acute hypoxia. Neither drug altered the slopes of ventilatory, sympathetic, or cardiovascular responses to acute hypoxia. We conclude that losartan and allopurinol are viable pharmacotherapeutic adjuncts for achieving blood pressure control in hypertensive OSA patients, even those who are adequately treated with CPAP.