In cerebrovascular circadian rhythms, EETs keep the beat. Focus on “Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature”

CIRCADIAN RHYTHMS PERMEATE virtually all life. In mammals, these rhythms are evident in circulating glucose and hormone levels, immune cell abundance and activity, whole body metabolic rate and temperature, and blood pressure. Correspondingly, the function and activity of all major organ systems also exhibit strong circadian rhythms. From a cardiovascular perspective, many of these functional oscillations are driven by circadian changes in the activity of the sympathetic nervous system and concomitant changes in systemic vascular reactivity. In the cerebral circulation, however, the contractile efficacy of the sympathetic perivascular innervation is limited (14), and thus other mechanisms must mediate the long-established circadian patterns in cerebral blood volume, blood flow, hypercapnic reactivity, and cerebral oxygen consumption (7). Daily oscillations in circulating glucocorticoids (12) or melatonin (5) may contribute to these cerebral rhythms, but the exact mediators remain uncertain and controversial.

From a clinical perspective, knowledge of the mechanisms mediating cardiovascular circadian rhythms is highly relevant to the management of patients at high risk for stroke and myocardial infarction. As recognized long ago, most adverse cardiovascular events occur early in the morning for reasons that remain poorly understood despite intensive investigation (4). A pragmatic response to this pattern has been to adjust the timing of pharmacotherapy for optimum efficacy in the early morning hours (2). Despite the success of these largely empirical chronopharmacologic strategies, fundamental advances in therapeutic management of these patients await deeper understanding of the mechanisms driving circadian rhythms.