Melatonin differentially affects vascular blood flow in humans

Abstract

Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

Fig. 1.

Vascular blood flow responses after melatonin and placebo ingestion. Melatonin (3 mg) significantly decreased renal blood flow velocity (RBFV) and renal vascular conductance (RVC), significantly increased forearm blood flow (FBF) and forearm vascular conductance (FVC), and did not alter cerebral blood flow velocity (MCA-BV) and cerebrovascular conductance (MCA-VC). Values are means ± SE. *P < 0.05, significantly different from placebo.

Fig. 2.

Renal vascular responses after melatonin ingestion (3 mg) and phentolamine (5-mg bolus). Melatonin significantly decreased RBFV and RVC. Phentolamine reversed these changes. Values are means ± SE. *Significantly different from baseline. †P < 0.002, significantly different from phentolamine infusion.