A quantitative study of the response to adenosine triphosphate of the blood vessels of the human hand and forearm

Duff, F. A.; Patterson, G. C.; Shepherd, John T.

doi:10.1113/jphysiol.1954.sp005182

Cited by 62 publications

(24 citation statements)

References 3 publications

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“…Underpinning the physiological relevance of circulating ATP, we found that the infusion of ATP in the femoral artery at rest in normoxia evoked a dosedependent increase in TBF and TVC comparable to that observed during exercise. This finding agrees with the wellcharacterized vasodilator effect of ATP infusion in the human forearm 25,26 and isolated arterioles 23,24 and extends previous results by directly comparing the hemodynamic effects of intraarterial infusion of ATP to those associated with endogenous ATP during exercise. The present observation that neither mean blood pressure nor blood flow in the control thigh were altered suggest that the infused ATP primarily acted locally.…”

Section: Similar Increase In Skeletal Muscle Hemodynamics With Intraasupporting

confidence: 90%

“…3 The vasodilator potency of ATP is clearly supported by reports where ATP was infused in isolated arterioles [21][22][23][24] and human forearm. 25,26 Although in vitro data demonstrate that ATP is released from red blood cells with exposure to hypoxia in the presence of hypercapnia, 27 hypoxia alone, 3 and mechanical deformation, 28 the physiological significance of this mechanism has never been studied in intact humans.…”

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confidence: 99%

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Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery

González‐Alonso

Olsen

Saltin

2002

Circulation Research

285

332

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Abstract-Blood flow to contracting skeletal muscle is tightly coupled to the oxygenation state of hemoglobin. To investigate if ATP could be a signal by which the erythrocyte contributes to the regulation of skeletal muscle blood flow and oxygen (O 2 ) delivery, we measured circulating ATP in 8 young subjects during incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and Key Words: skeletal muscle blood flow Ⅲ erythrocytes Ⅲ oxygen sensor Ⅲ oxygen delivery T he signals regulating the rapid adjustments of skeletal muscle blood flow to exercise and altered inspiratory O 2 fraction have been the focus of more than a century of research. Recently, the idea has been advanced that optimal local circulatory adjustments to alterations in blood oxygenation and exercise require the existence of extracellular and cellular O 2 sensors coupled to signal-transduction systems, which are capable of evoking the appropriate vascular responses in contracting and resting muscle. 1-9 The extensive available evidence demonstrating that alterations in circulating O 2 are inversely related to changes in exercising skeletal muscle blood flow provides indirect support for this notion. 10 -20 To assess the primary extracellular site of O 2 sensing, this laboratory's initial approach was to elucidate whether alterations in skeletal muscle blood flow to exercise in humans were associated with either the amount of O 2 dissolved in circulating plasma or the amount of O 2 bound to hemoglobin. 16,19 Using normoxia, hypoxia, anemia, anemiaϩhypoxia, COϩnormoxia, and COϩhyperoxia as interventions, we found compelling evidence indicating that elevations in exercising muscle blood flow and vascular conductance are independent of pronounced alterations in PaO 2 (40 to 540 mm Hg) but are closely linked to the reductions in arterial oxyhemoglobin. 16,19 Our findings suggest that the main vascular O 2 sensor locus is located in the erythrocyte itself, rather than in the PO 2 sensitive regions of the endothelium or vascular smooth muscle.The red blood cell itself might be involved in the regulation of local blood flow and O 2 delivery by signaling O 2 availability in the erythrocyte. This theory is consistent with the findings from two independent groups of researchers who have demonstrated that red blood cells release ATP 3 and NO 4,5 in response to a fall in hemoglobin O 2 saturation. The release of NO from the S-nitrosohemoglobin molecule with the lowering in oxyhemoglobin is thought to induce the diffusion of the NO group to the vascular endothelium where it stimulates vessel relaxation. 4 -5 ATP in turn can induce vasodilatation by binding to P 2y -purinergic receptors located on the vascular endothelial cells to release NO-and/or endothelium-derived hyperpolarization factors, which diffuse to the vascular smooth muscle and result in vasodilatation. 3 The vasodilator potency of ATP is clearly supported by Original

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Section: Similar Increase In Skeletal Muscle Hemodynamics With Intraasupporting

confidence: 90%

mentioning

confidence: 99%

Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery

González‐Alonso

Olsen

Saltin

2002

Circulation Research

285

332

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“…ATP is an attractive mediating signal for skeletal muscle blood‐flow regulation, not only because it can act as a potent vasodilator capable of increasing leg perfusion by up to ∼8 l min −1 (Duff et al . 1954; González‐Alonso et al . 2002, 2008), but also because of its sympatholytic properties in the human limb circulation (Rosenmeier et al .…”

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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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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“…ATP may contribute to the attenuation of cutaneous vasoconstrictor responsiveness in heat-stressed subjects since it is coreleased from multiple nerve types in humans and animals (1,2,5,18,29,36), has sympatholytic effects in human skeletal muscle (13,21), and dilates the cutaneous vasculature (6). However, in order for ATP to attenuate the effectiveness of the cutaneous vasoconstrictor system in heat-stressed subjects, it must be coreleased from sympathetic cholinergic nerves during a heat stress.…”

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confidence: 98%

Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

Wingo

Brothers

Coso

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic "active" vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is co-released from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean +/- SD; 35 +/- 11 years). Local temperature at each site was clamped at 34 degrees C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to approximately 42 degrees C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1 x 10(-4) M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 +/- 26% CVC(peak) units and by 36 +/- 15% CVC(peak) units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

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A quantitative study of the response to adenosine triphosphate of the blood vessels of the human hand and forearm

Cited by 62 publications

References 3 publications

Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery

Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery

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

Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

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