Melatonin Supplementation in Hypertensive Patients

在美国，高血压影响着大约5000万人，是引发不良心血管事件的主要危险因素。β-受体阻滞剂是治疗高血压、心绞痛和心律失常的一线药物。β-受体阻滞剂的副作用包括夜间失眠和白天疲劳。因为褪黑激素有促进睡眠的作用，所以β-受体阻滞剂对夜间褪黑激素的抑制可能与这些副作用有关。因此，主要的临床目的是确定在接受β-受体阻滞剂治疗的高血压患者中，夜间补充褪黑激素是否可以逆转这些副作用。最近在高血压患者中发现了昼夜节律系统的解剖和生理紊乱。由于褪黑素可以放大甚至恢复紊乱的昼夜节律，我们最近研究了补充褪黑素对未接受β-受体阻滞剂治疗的高血压患者夜间睡眠和血压的潜在有益影响。我们证明，3周夜间补充褪黑素显著增加了总睡眠时间和睡眠效率，并降低了血压。因此，在药物抑制褪黑激素水平的高血压患者中(即，通过β-受体阻滞剂治疗)，补充褪黑激素可能更有益。本提案的长期目标是研究夜间补充褪黑素作为对抗β-受体阻滞剂副作用的有效性。这项研究旨在验证这样一种假设，即接受β-受体阻滞剂治疗的高血压患者在夜间补充3周的褪黑素：1)改善睡眠数量和质量，2)帮助降低血压。我们建议在一项随机的、安慰剂对照的双盲研究中，通过比较补充3周(褪黑素/安慰剂)前、中、后的生理变量来研究这些假说。这项建议可能有助于开发针对β-受体阻滞剂副作用的失眠对策。此外，补充夜间被抑制的褪黑素水平可能会导致一种治疗高血压的新策略。

Hypertension affects approximately 50 million individuals in the United States and constitutes a prime risk factor for adverse cardiovascular events. beta-Blockers constitute first-line therapy in the treatment of hypertension, angina, and arrhythmia. Side-effects of beta-blockers include nighttime insomnia and daytime fatigue. Because melatonin has a sleep promoting action, the suppression of nighttime melatonin by beta-blockers may be involved in those side-effects. Thus, the primary clinical aim is to determine if these side-effects may be reversed by nighttime melatonin supplementation in hypertensive patients treated with beta-blockers. Anatomical and physiological disturbances of the circadian system have recently been shown in patients with essential hypertension. Because melatonin can amplify and even restore disturbed circadian rhythmicity, we recently investigated the potential beneficial effect of melatonin supplementation on nighttime sleep and BP in patients with essential hypertension who were not treated with beta-blockers. We demonstrated that 3-week nighttime melatonin supplementation significantly increased total sleep time and sleep efficiency, and decreased BP. Thus, in hypertensive patients with pharmacologically suppressed melatonin levels (i.e., by beta-blocker therapy), melatonin supplementation may be even more beneficial. The long-term objective of the present proposal is to investigate the efficacy of nighttime melatonin supplementation as a counter measure against side-effects of beta-blockers. The study is designed to test the hypothesis that 3-week nighttime melatonin supplementation in hypertensive patients treated with beta-blockers: 1) improves sleep quantity and quality and 2) assists in lowering BP. We propose to investigate the hypotheses in a randomized, placebo-controlled, double blind study by comparing the physiological variables before, during, and after 3-week (melatonin/placebo) supplementation episodes. This proposal may assist in developing counter measures against insomnia as side-effect of beta-blockers. Furthermore, supplementation of suppressed nighttime melatonin levels may lead to a novel strategy in the treatment of essential hypertension.