A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endotheliumdependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 Ϯ 4 vs. 15 Ϯ 2 arbitrary units and 29 Ϯ 6% vs. 12 Ϯ 6%, respectively, P Ͻ 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 Ϯ 8 vs. 65 Ϯ 10 EMPs/l, P Ͻ 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity. dry immersion; weightlessness; microcirculation; endothelial dysfunction; soluble endothelial markers THE VASCULAR ENDOTHELIUM is a key element in the control of local blood flow (12,46). It is now widely recognized that alterations of endothelial integrity and physiological functions represent pivotal mechanisms in the initiation and development of vascular diseases. A decrease in endothelial vasomotor function (endothelium-dependent vasodilation), which correlates with a risk of cardiovascular events, has been demonstrated in patients with atherosclerosis, hypertension, and peripheral vascular diseases (49). Physical inactivity and a sedentary lifestyle are known to cause cardiovascular deconditioning and increase the risk of cardiovascular disease (5). Endothelial dysfunction seems to be intimately linked to this deconditioning. A chronic decrease in shear stress forces during physical inactivity, especially significant in small vessels of the microcirculatory bed (8), may impair endothelial functions.Experimental physical inactivity of varying duration and intensity in healthy humans can be achieved through confinement (altitude chambers), partial immobilization, bedrest, and "dry" water immersion (33, 34). Dry immersion (DI) induces extreme physical inac...

Sedentary behavior has deleterious effects on the cardiovascular system, including reduced endothelial functions. A 2-mo bed rest study in healthy women [women international space simulation for exploration (WISE) 2005 program] presented a unique opportunity to analyze the specific effects of prolonged inactivity without other vascular risk factors on the endothelium. We investigated endothelial properties before and after 56 days of bed rest in 8 subjects who performed no exercise (control group: No-EX) and in 8 subjects who regularly performed treadmill exercise in a lower body negative pressure chamber as well as resistance exercise (countermeasure group, EX). A functional evaluation of the microcirculation in the skin was assessed with laser Doppler. We studied endothelium-dependent and -independent vasodilation using iontophoresis of acetylcholine and sodium nitroprusside, respectively. We also measured circulating endothelial cells (CECs), an index of endothelial damage. In the No-EX group, endothelium-dependent vasodilation was significantly reduced (35.4 +/- 4.8% vs. 24.1 +/- 3.8%, P < 0.05) by bed rest with a significant increase in the number of CECs (3.6 +/- 1.4 vs. 10.6 +/- 2.7 ml(-1), P < 0.05). In the EX group, endothelium-dependent vasodilation and number of CECs were preserved. Our study shows that in humans prolonged bed rest causes impairment of endothelium-dependent function at the microcirculatory level, along with an increase in circulating endothelial cells. Microcirculatory endothelial dysfunction might participate in cardiovascular deconditioning, as well as in several bed rest-induced pathologies. We therefore conclude that the endothelium should be a target for countermeasures during periods of prolonged deconditioning.

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