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.?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT002713-01
Application #
6902417
Study Section
Special Emphasis Panel (ZAT1-JH (05))
Program Officer
Wong, Shan S
Project Start
2005-09-01
Project End
2008-06-30
Budget Start
2005-09-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$157,500
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Scheer, Frank A J L; Hilton, Michael F; Mantzoros, Christos S et al. (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A 106:4453-8
RĂ¼ger, Melanie; Scheer, Frank A J L (2009) Effects of circadian disruption on the cardiometabolic system. Rev Endocr Metab Disord 10:245-60
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Scheer, Frank A J L; Shea, Thomas J; Hilton, Michael F et al. (2008) An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night. J Biol Rhythms 23:353-61