Night shift and impaired endothelial function: Circadian out-of-synch may play a role

The interesting study by Kim et al. reported a significant decrease in nitric oxide (NO) in a group of healthy female nurses after three sequential night shift. This study is in agreement also with a recent study by Suessenbacher et al., who also demonstrated a reduced peripheral arterial tone in shift workers compared with nonshift workers. The authors state that night shift work might be a stressor capable to deteriorate flow-mediated brachial artery dilation (FMD), but the precise mechanism is unknown. On one hand, the existence of a circadian variation in basal vascular tone, due at least in part to increased alpha-sympathetic vasoconstrictor activity, has been demonstrated, and this could play a role in the complex series of triggering factors potentially favoring the higher incidence of acute cardiac ischemic events in the morning. On the other hand, a recent growing body of evidence has shown that vascular function and circadian clocks are tightly coupled. Circadian clocks exist as a self-sustained transcriptional-translational circuit consisting of positive and negative feedback loops, and generating a rhythm in gene expression with a period of approximately 24 hours. The principal (master) circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and is entrained by light, but peripheral circadian clocks have been identified within almost all mammalian cell types, including cardiomyocytes, vascular smooth muscle cells, and endothelial cells. The principal role of cellular biological clocks is driving circadian rhythms to adapt the organism to further needs in an anticipatory manner, so providing selective advantage. However, it has been recently shown that external or internal disruption (dyssinchrony) of circadian control may result in overt diseases. For example, mice exposed to a 20-hour instead of 24-hour circadian rhythm show a complete disruption of sleep/wake behavior and a marked progression of myocyte hypertrophy and fibrosis. Again, bmal1 knockout mice or clock mutant mice exhibit impairment of normal protective endothelial responses to vascular injury with pathological remodeling and predisposition to vascular thrombosis, and mice with mutation in the Per2 gene show endothelial disfunction characterized by decreased production of NO and vasodilatory prostaglandins, and increased release of cyclooxygenase-1-derived vasoconstrictor substances. Thus, it is quite likely that vascular and endothelial function and NO production may be affected and impaired in night shift workers via a circadian-based mechanism. Now, we have no conclusive data on whether out-of-synch of biological clocks may influence health or disease, and which amount of circadian rhythm disruption or sleep deprivation may be harmful for the cardiovascular system. For example, it has been found that the incidence of acute myocardial infarction was slightly (but significantly) increased for the first three weekdays after the transition to daylight saving time in the spring, with an incidence ratio of 1.051 for the first week. Finally, several risk factors have to be considered when evaluating shift work disorder, e.g., age, female sex, time of light exposure, duration of the shift, familial (genetic) predisposition, and so on. The results reported by Kim et al have been obtained after a sequential series of three night shifts, and rapid shift rotation is suggested to not allow bodily's rhythms to synchronize to a new schedule. In conclusion, keeping away from alarmistic manipulations, it is undoubtful that circadian rhythms play an important role in cardiovascular health and disease, and further studies on night shift-workers should be addressed to clarify potential cardiovascular effects of possible rhythm disruption.