Regulation of skeletal muscle blood flow during exercise in ageing humans

Abstract

The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium‐derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age‐associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium‐derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin‐1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. ‘functional sympatholysis’), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium‐dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age‐associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium‐dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans.

Effect of high-intensity exercise training on functional sympatholysis in young and older habitually active men

“…Functional sympatholysis is thought to have an important role in opposing the increased sympathetic drive and thereby vasoconstriction in the exercising muscle . In the current study, tyramine infusion lowered LVC during exercise at both low (6 W) and moderate (50% W max) intensity to a similar extent in the young and older groups, suggesting a similar ability for sympatholysis in the two groups.…”

Matched increases in cerebral artery shear stress, irrespective of stimulus, induce similar changes in extra-cranial arterial diameter in humans

“…Indeed, functional sympatholysis is a well-established phenomenon in skeletal muscle arterioles during exercise. 21,22 Ultimately, vasomotor drive to vascular smooth muscle, in response to a stimulus as complex and integrative as exercise, will reflect the balance between dilator and constrictor mechanisms and our study supports a role in this regard for shear-mediation vasodilation.…”

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

“…As blood carries oxygen to the active muscle, skeletal muscle blood flow is a major determinant of O 2 supply and can therefore impact O 2 utilization. Indeed, limited blood flow to active skeletal muscles has been implicated as an important factor that contributes to the decline in exercise capacity associated with the aging process [72]. Such limitations promote a sedentary lifestyle with advancing age, and it is now well established that physical inactivity represents an independent risk factor for many cardiovascular diseases [73], including HF.…”