Circulating ATP‐induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle

New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (trueV˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb trueV˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙normalO2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb trueV˙O2, whereas ABF, arm T B and V˙normalO2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in trueV˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, T B and aerobic metabolism in exercising and non‐exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V˙normalO2 contribute to the regulation of limb perfusion through control of intravascular ATP.

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“…2002, 2008), but also because of its sympatholytic properties in the human limb circulation (Rosenmeier et al . 2004; Kirby et al . 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The increased vasodilatation in the legs occurred despite a higher plasma noradrenaline concentration, indicating that the high ATP and/or other vasoactive substance overrode the effect of enhanced vasoconstrictor activity in the leg (Rosenmeier et al . 2004; Kirby et al . 2008).…”

Section: Discussionmentioning

confidence: 99%

Blood temperature and perfusion to exercising and non‐exercising human limbs

González‐Alonso

Calbet

Boushel

et al. 2015

Experimental Physiology

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“…54 Release of adenosine tri-phosphate (ATP) by erythrocytes exposed to low oxygen tension 55 and by endothelial cells (as a response to hypoxia and shear stress), 56 contributes to skeletal muscle vasodilation by leading to the release of vasoactive substances and diminishing sympathetic vasoconstriction. 57,58 Adenosine appears to also play a major role, as in vivo injection of adenosine in the femoral artery leads to leg arterial vasodilation similar to that with exercise; also, adenosine receptor blockade reduces blood flow to the lower limbs during exercise. 59 Adenosine receptors are present in the endothelium and vascular smooth muscle cells of skeletal muscle arteries, and formation of nitric oxide and prostaglandins, known vasodilators, appears to be the mechanism underlying adenosine's regulation of skeletal muscle blood flow.…”

Section: Regulation Of Blood Flow To the Lower Limbsmentioning

confidence: 99%

Arterial dysfunction and functional performance in patients with peripheral artery disease: A review

2011

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Functional performance influences quality of life in individuals with peripheral artery disease (PAD) and is also a powerful prognostic marker in these patients. The pathophysiology of impaired functional performance in patients with PAD is incompletely understood. The severity of atherosclerotic burden, non-invasively assessed by the ankle-brachial index (ABI), does not reliably predict the degree of functional impairment observed in PAD patients. We review associations of measures of arterial function (arterial stiffness and endothelial dysfunction) with functional performance in PAD patients, and also review potential therapies for arterial stiffness and endothelial dysfunction that could improve functional performance in PAD. Recent studies suggest that measures of arterial function, such as arterial stiffness and endothelial function, are associated with exercise performance in the setting of PAD. These studies have provided new insights into (1) the pathophysiology of functional impairment in PAD, (2) mechanisms of strategies known to be effective such as walking programs, and (3) potential new therapeutic interventions for improving functional performance. Thus, therapies aimed at arterial 'de-stiffening' and improving endothelial function (such as aerobic exercise, statins and angiotensinconverting enzyme inhibitors) may improve functional performance in patients with PAD; however, further investigations are needed.

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“…The exact nature of the dilator factors that are active during exercise is not clear (27). Some data do suggest a key role for arterial hyperpolarization, such as the sensitivity of muscle fiber contraction-mediated dilation to glibenclamide (4,24), an inhibitor of ATP-sensitive K ϩ channels (and ABC transporters), and the release of ATP into the lumen of arteries during exercise (26). ATP is released in response to low PO 2 [from red blood cells (8,9)] and may have a key role in regulating tissue perfusion.…”

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confidence: 99%

Does arterial myogenic tone determine blood flow distribution in vivo?

Dora¹

2005

American Journal of Physiology-Heart and Circulatory Physiology

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BLOOD FLOW DISTRIBUTION at rest and during exercise is intricately controlled by centrally driven neuroeffector mechanisms and circulating hormones (particularly epinephrine), local autacoids, and metabolites, all superimposed on the inherent or "myogenic" reactivity of the arterial smooth muscle. During exercise, the cardiac output of a trained athlete can increase ϳ5-fold, and these mechanisms serve to coordinate a huge (ϳ20-fold) increase in the amount of blood routed to the exercising muscle (3). The dramatic nature of this increase is illustrated by the fact that the proportion of the cardiac output diverted to skeletal muscle can change from 20% to ϳ80%! Importantly, and to the benefit of the individual, despite this enormous increase in the flow of blood to muscle, brain blood flow is not compromised (3). But to what extent do the inherent characteristics of the arteries of the brain and musculature explain these distinct changes?As cerebral arteries are not particularly responsive to the sympathetic nerves surrounding them, myogenic reactivity is thought to be a fundamental determinant of the constant flow of blood to the brain and, as a consequence, has been extensively studied. The most direct studies have assessed how changes in intraluminal pressure links to smooth muscle contraction/relaxation in isolated arteries, where reflex and most local influences are absent and steady-state conditions can be achieved. It is technically extremely difficult to make intracellular recordings from the very small (Ͻ10 m width) smooth muscle cells, particularly in isolated arteries under physiological pressure. However, a now classic study in 1984 by Harder (13) first showed that increasing pressure alone caused depolarization and as a result stimulated Ca 2ϩ influx and vasoconstriction. Unfortunately, technology at the time did not allow accurate simultaneous measurement of diameter. This was achieved in later studies, notably from Nelson's group (19), as the complexity of the myogenic control mechanism became apparent. It is now known that voltage-activated calcium entry is not the only mechanism responsible for changes in myogenic tone (16) and that the relative contributions from different mechanisms vary between and within vascular beds.In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Kotecha and Hill (21) are the latest to attempt the extremely difficult task of quantifying the importance of membrane potential for myogenic reactivity, but this time in a resistance artery from a striated muscle bed (the rat cremaster muscle, pressurized arteries with a passive diameter of ϳ140 m at 70 mmHg). This is the first study in a muscle resistance artery that has attempted to assess the effect of a stepwise increase in luminal pressure on smooth muscle membrane potential and arterial diameter. In addition, the authors have compared their data with published data from rat isolated cerebral arteries [distal posterior, passive diameter of ϳ200 m at 70 mmHg (19)] to attempt to reveal how...

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Circulating ATP‐induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle

Cited by 161 publications

References 69 publications

Blood temperature and perfusion to exercising and non‐exercising human limbs

Blood temperature and perfusion to exercising and non‐exercising human limbs

Arterial dysfunction and functional performance in patients with peripheral artery disease: A review

Does arterial myogenic tone determine blood flow distribution in vivo?

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