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      The effect of melatonin on circadian blood pressure in patients with type 2 diabetes and essential hypertension

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          Abstract

          Introduction

          The aim of this study was to evaluate the effect of melatonin on blood pressure in patients with essential hypertension receiving medical treatment and with type 2 diabetes in good metabolic control.

          Material and methods

          The study lasted 8 weeks. Patients were equipped with a 24-hour ambulatory blood pressure monitor and took melatonin (3 mg a day in the evening) for 4 weeks. The patients were divided into four groups: group 1 ( n = 32) including dippers, group 2 ( n = 34) non-dippers treated with melatonin; and two control groups: group 3 ( n = 28) including dippers and group 4 ( n = 30) non-dippers treated without melatonin. After 4 weeks patients took melatonin for the next 4 weeks (5 mg a day). In each visit were analyzed: systolic, diastolic and mean blood pressure in both day and night time.

          Results

          We observed that 29.5% non-dippers ( n = 10) treated with melatonin in a dose of 3 mg/day achieved features of dippers compared to control group ( p < 0.05). Five mg of melatonin per day restored normal diurnal blood pressure rhythm in 32.4% non-dippers ( n = 11, p < 0.05). In non-dippers treated with melatonin significant decreases of diastolic, systolic and mean night blood pressure values ( p < 0.05) were observed.

          Conclusions

          More than 30% of non-dippers with type 2 diabetes treated with melatonin were restored to the normal circadian rhythm of blood pressure. The effect of melatonin in both doses (3 mg and 5 mg) was significant for non-dippers only and included nocturnal systolic, diastolic and mean arterial pressure.

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          Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

          J. Staessen, L. Thijs, R. Fagard … (1999)
          The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. Family practices and outpatient clinics at primary and secondary referral hospitals. A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.
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            Identification of the melatonin-binding site MT3 as the quinone reductase 2.

            O Nosjean, M. Ferro, F Coge … (2000)
            The regulation of the circadian rhythm is relayed from the central nervous system to the periphery by melatonin, a hormone synthesized at night in the pineal gland. Besides two melatonin G-coupled receptors, mt(1) and MT(2), the existence of a novel putative melatonin receptor, MT(3), was hypothesized from the observation of a binding site in both central and peripheral hamster tissues with an original binding profile and a very rapid kinetics of ligand exchange compared with mt(1) and MT(2). In this report, we present the purification of MT(3) from Syrian hamster kidney and its identification as the hamster homologue of the human quinone reductase 2 (QR(2), EC ). Our purification strategy included the use of an affinity chromatography step which was crucial in purifying MT(3) to homogeneity. The protein was sequenced by tandem mass spectrometry and shown to align with 95% identity with human QR(2). After transfection of CHO-K1 cells with the human QR(2) gene, not only did the QR(2) enzymatic activity appear, but also the melatonin-binding sites with MT(3) characteristics, both being below the limit of detection in the native cells. We further confronted inhibition data from MT(3) binding and QR(2) enzymatic activity obtained from samples of Syrian hamster kidney or QR(2)-overexpressing Chinese hamster ovary cells, and observed an overall good correlation of the data. In summary, our results provide the identification of the melatonin-binding site MT(3) as the quinone reductase QR(2) and open perspectives as to the function of this enzyme, known so far mainly for its detoxifying properties.
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              Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study.

              Hiroshi Satoh, K. Nagai, A Aihara … (1997)
              To investigate the relation between nocturnal decline in blood pressure and mortality, we obtained ambulatory blood pressures in 1542 residents aged 40 years or over of a rural Japanese community. Subjects were followed-up for a mean of 5.1 years and were then subdivided into four groups according to the percent decline in nocturnal blood pressure: 1) extreme dippers: percent decline in nocturnal blood pressure > or = 20% of the daytime blood pressure; 2) dippers: decline of > or = 10% but or = 0% but < 10%; and 4) inverted dippers: no decline. The relationship between the decline in nocturnal blood pressure and mortality was examined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, previous history of cardiovascular disease, and the use of antihypertensive medication. The mortality risk was highest in inverted dippers, followed by nondippers. There was no difference in mortality between extreme dippers and dippers. This relationship was observed for both treated and untreated subjects, was more pronounced for cardiovascular than for noncardiovascular mortality, and did not change after the data were adjusted for 24-h, daytime, and nighttime blood pressure levels.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Arch Med Sci
                Journal ID (iso-abbrev): Arch Med Sci
                Journal ID (publisher-id): AMS
                Title: Archives of Medical Science : AMS
                Publisher: Termedia Publishing House
                ISSN (Print): 1734-1922
                ISSN (Electronic): 1896-9151
                Publication date (Electronic): 29 August 2014
                Publication date (Print): 29 August 2014
                Volume: 10
                Issue: 4
                Pages: 669-675
                Affiliations
                [1 ]Department of Internal Medicine and Clinical Pharmacology, Medical University of Lodz, Poland
                [2 ]University Teaching Hospital No. 2, Lodz, Poland
                Author notes
                Corresponding author: Monika Możdżan MD, PhD, Department of Internal Medicine and Clinical Pharmacology, Medical University of Lodz, 1/5 Kniaziewicza St, 91-347 Lodz, Poland. Phone: +48 695 88 31 54. E-mail: monika.mozdzan@ 123456umed.lodz.pl
                Article
                Publisher ID: 23418
                DOI: 10.5114/aoms.2014.44858
                PMC ID: 4175768
                PubMed ID: 25276149
                SO-VID: bc913e1c-37aa-4fe7-b643-d8b18fab307f
                Copyright © Copyright © 2014 Termedia & Banach
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 January 2012
                Date revision received : 21 March 2012
                Date accepted : 11 May 2012
                Categories
                Subject: Clinical Research

                ScienceOpen disciplines: Medicine
                Keywords: non-dipping,melatonin,ambulatory blood pressure monitoring
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: non-dipping, melatonin, ambulatory blood pressure monitoring

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