The circadian melatonin rhythm and its modulation: possible impact on hypertension

In experimental rodents, surgical removal of the pineal gland, the major source of circulating melatonin, causes a gradual and sustained rise in blood pressure. Conversely, when melatonin is chronically administered to pinealectomized rodents the increment in blood pressure is ameliorated. In humans as well, the night time rise in endogenous circulating melatonin levels may be inversely related to the reduction in night time blood pressure. Among patients with hypertension, some exhibit a much greater reduction in blood pressure at night (the so-called 'extreme dippers' and 'dippers'), whereas others exhibit only a slight night time reduction in systolic and diastolic pressure ('non-dippers' and 'inverted dippers'). Longitudinal studies of these patients show that inverted dippers and non-dippers die at a faster rate than do dippers and extreme dippers. The chronic administration of melatonin to individuals with hypertension induces a measurable drop in night time systolic and diastolic blood pressure. Moreover, the higher the night time level of endogenous melatonin (estimated from urinary metabolite of melatonin, 6-hydroxymelatonin sulphate), the greater the reduction in arterial blood pressure at night. The implication of these findings is that melatonin may have utility as an antihypertensive agent.