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No Influence of Melatonin on Cerebral Blood Flow in Humans

Section of Gerontology and Geriatrics, Department of General Internal Medicine (A.H.M.v.d.H.-v.M., A.J.M.d.C., G.J.B.), and Department of Radiology (R.v.d.B., M.A.v.B.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research and Institute for Clinical and Experimental Neuroscience, Vrge Universiteit Medical Center (E.J.W.v.S.), 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Eus J. W. van Someren, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ, Amsterdam, The Netherlands. E-mail: e.van.someren{at}nih.knaw.nl.

Melatonin has been attributed a role in a number of physiological processes. Changes in distal skin temperature and blood pressure after intake of melatonin suggest that melatonin induces peripheral vasodilation. The effect on the cerebral blood flow is still unknown. We examined the effect of a single pulse of melatonin on cerebral and peripheral blood flow, using the latter as a positive control. Ten male healthy volunteers (mean age, 22 ± 3.2 yr) participated in a double-blind, randomized, placebo-controlled, cross-over study. On one occasion 10 µg melatonin were infused iv, and on the other occasion saline was infused as the matching placebo. Cerebral blood flow was measured using phase contrast magnetic resonance imaging. Peripheral blood flow was determined from changes in the distal to proximal skin temperature gradient and finger pulse volume. Serum melatonin concentration increased from 12 ± 5 pg/ml at baseline to 487 ± 377 pg/ml at 5 min and 156 ± 68 pg/ml at 10 min after melatonin administration. There was no significantly different time course for cerebral blood flow and cerebrovascular resistance. Compared with placebo, melatonin significantly increased peripheral blood flow, as measured by distal to proximal skin temperature gradient and finger pulse volume. These data demonstrate that melatonin does not have an acute regulatory effect on cerebral blood flow in humans.

This work was supported by grants from the Netherlands Institute for Brain Research and Vrge Universiteit Medical Center, Netherlands Organisation for Health Research and Development (The Hague, The Netherlands; Project 28-3003), Netherlands Organisation for Scientific Research (The Hague, The Netherlands; Projects SOW 014-90-001 and Vernieuwingsimpuls), Stichting Centraal Fonds RVVZ, Japan Foundation for Aging and Health (to E.J.W.v.S.); and Bristol-Myers Squibb (Princeton, NJ; to A.H.M.v.d.H.-v.M. and G.J.B.).

Abbreviations: CBF, Cerebral blood flow; DPG, distal to proximal skin temperature gradient; ECG, electrocardiogram; MAP, mean arterial pressure; MRI, magnetic resonance imaging; PAT, peripheral arterial tone; PBF, peripheral blood flow.