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1	I’ve got rhythm…Circadian rhythm Melatonin & Hypertension Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit The Chaim Sheba Medical Center, Tel-Hashomer Sackler Faculty of Medicine, Tel Aviv University
2	“The pineal gland is the seat of the soul” René Descartes
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4	"Melatonin is known as a..." Melatonin is known as a stringent biological modulator of mood, sleep, retinal physiology, sexual behavior, seasonal-reproductive physiology and behavior, circadian rhythms, and immunologic function .
5	Physiological effects of melatonin
6	Melatonin receptors G coupled protein M1 M2 subtypes Primarily - within CNS: SCN, PVN, Postrema Also in CVS: aorta, coronary arteries, cardiomyocytes Additional intracellular effects
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8	Central SNS depressant
9	Increase BRS
10	SNS peripheral
11	Increased endothelial NOS via endothelial iCa
12	Increased ROS
13	Pathophysiological significance of melatonin
14	"Experimental evidence point to the..." Experimental evidence point to the influence of melatonin on aging and age-related processes and disease states In the last decades, some works had shown evidence that melatonin has influence in cardiovascular processes, including hypertension.
15	Melatonin and abnormal 24 H BP
16	Melatonin and non dippers
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18	Non dippers have less melatonin at night
19	Melatonin and Metabolic Syndrome
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21	Aims of study To evaluate the relationship between melatonin secretion and the evolving of hypertension in rats with metabolic syndrome. 2. To assess whether adding exogenous melatonin to those rats prevents hypertension.
22	Study design
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24	Results Fructose +/- saline induced the metabolic syndrome
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26	Melatonin excretion during sleep time (ng/mgCr)
27	Effect of Melatonin
28	Therapeutic use
29	"Melatonin deficiency may play a..." Melatonin deficiency may play a role in the pathogenesis of impaired nocturnal BP fall.
30	In essential HTN? Premature !!
31	In nocturnal HTN?
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33	Patients and Methods Treated hypertensive patients who had an Ambulatory Blood Pressure Monitoring (ABPM) as part of their routine evaluation, and had nocturnal hypertension (mean nighttime systolic BP > 125 mmHg) were screened and enrolled for the study.
34	Patients and Methods Of the 54 patients enrolled 38 patients (22 males, mean age 64 ± 11 years, ranged 42-83 years) were randomized and finally concluded the study. All patients were taking stable doses of antihypertensive medications during the last 2 months before and throughout the study.
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38	Conclusions An addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension
39	Night HTN
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41	Future perspective of use of melatonin
42	TOD: MI
43	TOD: Kidney
44	TOD: Kidney
45	TOD: Kidney
46	TOD CVA
47	TOD CVA
48	Summary Melatonin is an endogenous hormone pivotal in various biological and circadian processes Has an important vascular effects via sympathetic, endothelial and anti-oxidative mechanisms Plays a role in nocturnal hypertension and metabolic syndrome Clinically proven to reduce night BP Potentially protective against target organs damage
49	Thank you