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1567697 
Journal Article 
Potential roles of melatonin and chronotherapy among the new trends in hypertension treatment 
Simko, F; Pechanova, O 
2009 
Yes 
Journal of Pineal Research
ISSN: 0742-3098
EISSN: 1600-079X 
47 
2 
127-133 
19570132 
WOS:000268664200002 
The number of well-controlled hypertensives is unacceptably
low worldwide. Respecting the circadian variation of blood pressure, nontraditional
antihypertensives, and treatment in early stages of hypertension are potential ways to improve
hypertension therapy. First, prominent variations in circadian rhythm are characteristic for
blood pressure. The revolutionary MAPEC (Ambulatory Blood Pressure Monitoring and Cardiovascular
Events) study, in 3000 adult hypertensives investigates, whether chronotherapy influences the
cardiovascular prognosis beyond blood pressure reduction per se. Second, melatonin, statins and
aliskiren are hopeful drugs for hypertension treatment. Melatonin, through its scavenging and
antioxidant effects, preservation of NO availability, sympatholytic effect or specific melatonin
receptor activation exerts antihypertensive and anti-remodeling effects and may be useful
especially in patients with nondipping nighttime blood pressure pattern or with nocturnal
hypertension and in hypertensives with left ventricular hypertrophy (LVH). Owing to its
multifunctional physiological actions, this indolamine may offer cardiovascular protection far
beyond its hemodynamic benefit. Statins exert several pleiotropic effects through inhibition of
small guanosine triphosphate-binding proteins such as Ras and Rho. Remarkably, statins reduce
blood pressure in hypertensive patients and more importantly they attenuate LVH. Addition of
statins should be considered for high-risk hypertensives, for hypertensives with LVH, and
possibly for high-risk prehypertensive patients. The direct renin inhibitor, aliskiren, inhibits
catalytic activity of renin molecules in circulation and in the kidney, thus lowering angiotensin
II levels. Furthermore, aliskiren by modifying the prorenin conformation may prevent prorenin
activation. At present, aliskiren should be considered in hypertensive patients not sufficiently
controlled or intolerant to other inhibitors of renin-angiotensin system. Third, TROPHY (Trial of
Preventing Hypertension) is the first pharmacological intervention for prehypertensive patients
revealing that treatment with angiotensin II type 1 receptor blocker attenuates hypertension
development and thus decreases the risk of cardiovascular events. 
aliskiren; chronotherapy; hypertension treatment; melatonin; prehypertension; statins