Sitting and endothelial dysfunction: The role of shear stress

Abstract

SummarySedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as ‘sitting without otherwise being active.’ This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions.

Arterial stiffness and sedentary lifestyle: Role of oxidative stress

“…In our sedentary people, urinary 8-iso-PGF 2α excretion before exercise training was higher (364 ± 142 pg/mg creatinine) than that reported in healthy or low-risk subjects [30]. This result is in agreement with the notion that sedentary lifestyle is characterized by an imbalance between pro-and anti-oxidant molecules [14,[42][43][44]. After 8 weeks of training program, urinary 8-iso-PGF 2α excretion rate decreased to 224 ± 92 pg/mg creatinine (−25.9% vs baseline), reinforcing the idea that physical activity exerts its favorable effects on endothelial function through a reduction of oxidative stress.…”

“…Oxidative stress may play a major role in the pathogenesis of endothelial dysfunction [14], and is generated by an imbalance between pro-and anti-oxidant molecules. In this study, we tried to correlate oxidative stress and AS in sedentary people, before and after high-amount, high-intensity exercise, previously proved to be beneficial on HDL levels [19].…”

“…Exercise training (ET) may delay the development of arterial stiffness by increasing shear stress and augmenting nitric oxide (NO) bioavailability [14].…”

Vasoconstrictor stimulus determines the functional contribution of myoendothelial feedback to mesenteric arterial tone

“…In vivo , endothelial sensing of shear stress, the tangential frictional force exerted by blood flowing across the cell surface, plays a dominant role in regulating tissue perfusion (Thosar et al . ; Baeyens et al . ; Chistiakov et al .…”

Higher levels of daily physical activity are associated with better skin microvascular function in type 2 diabetes—The Maastricht Study

“…Mechanistically, higher levels of physical activity and lower levels of sedentary time are thought to increase nitric oxide bioavailability, presumably in conjunction with beneficial effects on low‐grade inflammation, both of which may improve microvascular (endothelial) function . As hyperglycemia has detrimental effects on nitric oxide bioavailability and microvascular (endothelial) function, the associations of physical activity and sedentary behavior with microvascular (endothelial) function may differ between (ie, may be stronger in) individuals with as compared to those without T2D.…”