Sleep deprivation is associated with an increase in sympathetic nervous system activity, blood pressure (BP) and pro-inflammatory status that may induce endothelial dysfunction, a key factor in the development of cardiovascular diseases. Mechanisms that link endothelial dysfunction to total sleep deprivation (TSD) are not actually known. The aim of our work was to assess the impact of TSD on vasomotricity and relationships with BP changes and immuno-inflammatory responses. In the first part, we observed, in healthy young men, that 40 hours TSD induce a decrease of acetylcholine (ACh)-induced vasodilatation and an increase in plasma levels of endothelial activation markers. This endothelial dysfunction appeared before the increase in BP and sympathetic activity and was associated with higher plasma levels of TNF-α, and TNF-α mRNA levels in white blood cells. In a second study, we showed that 29 hours TSD induce a decrease in digital skin temperature and vascular conductance during a cold water immersion test (30 min, 5°C bath) and during the subsequent passive rewarming. This decrease of local tolerance to cold, found without modification in BP and central temperature, was associated with an increase of plasma levels of endothelin-1. In the second part, we demonstrated that the decrease of endothelial- and current- induced vasodilation observed after 24 hours of awaking were independent of BP changes, in sympathectomised (reserpined) rats. We also observed a decrease of NO and prostacyclines (PGI2) pathways activity after TSD. These results were associated with an increase in plasma levels of TNF-α, and IL-6. In conclusion, our results suggest that TSD, in healthy subjects, is a sufficient stress to trigger an endothelial dysfunction and low grade inflammation, leading to a decrease in vascular reactivity. This phenomenon is initially independent on changes in BP and sympathetic activity and is the consequence of immuno-inflammatory responses.
