[The effect of long-term beta-blockers on melatonin secretion, sleep quality, and vascular brain damage].

Circadian rhythm of pineal melatonin production is paced by the thalamus suprachiasmatic nucleus (SCN) depending on the lighting conditions via signal transduction to pinealocytes beta-receptors. Melatonin is a natural regulator of many physiological processes, and the decrease of its synthesis leads to various diseases, in particular, insomnia and metabolic disorders. It is known that administration of beta-blockers reduces melatonin production, but the data showing clinical significance of melatonin reduction associated with beta-blockers administration are still contradictory. OBJECTIVE The influence of long-term administration of beta-blockers to melatonin synthesis, sleep quality and vascular brain damage. MATERIALS AND METHODS The main study group included 114 patients, aged 47-83, with cardiovascular diseases, who were under a complex therapy with long-term administration of beta-blockers. The comparison group included 110 patients with cardiovascular diseases, similar in age and sex, who did not receive beta-blockers in their complex therapy. The circadian dynamics of melatonin synthesis was observed by excretion of 6-sulfatoxymelatonin (6-SM), the major metabolite of melatonin, in three urinary samples (day, evening, night). All the patients underwent night polysomnography to assess the severity of sleep disorders. The severity of vascular brain damage was assessed using magnetic resonance imaging. RESULTS The analyses showed large variability in individual values of 6-SM circadian excretion of patients with cardiovascular diseases (from 0.9 to 133 μg/24h with a mid-point 16.8 μg/24h). A considerable decrease of 6-SM circadian excretion is detected in the group of patients taking beta-blockers comparing to those not Me [q 25; q 75]: 12.8 [6.2; 21.1] and 24.0 [12.5; 41.5] μg/24h, respectively (p<0.001), with no differences in sleep values and severity of vascular brain damage. Comparing subgroups of patients with 6-SM circadian excretion lower and higher than 16.8 μg/24h showed a significant increase of sleep latency, decrease of rapid eye movement sleep (REM sleep), increasing number of gliosis foci in white matter of the brain with higher values of leptin, leptin/adiponectin ratio and glycohemoglobin in the group of patients with 6-SM circadian excretion ≤16.8 μg/24h. CONCLUSION A low level of endogenous melatonin is a risk factor for development of sleep structure and quality disorders, vascular white matter brain damages with a higher risk for metabolic disorders. Long-term beta-blockers administration decrease endogenous melatonin synthesis to 50% increasing the risk for insomnia and vascular brain damage, mostly in patients with lower initial level of 6-SM circadian excretion.: melatonin, 6-sulfatoxymelatonin, beta-blockers, insomnia, vascular white matter brain damage, leptin, adiponectin.