Endothelium‐dependent vasodilatory signalling modulates α<sub>1</sub>‐adrenergic vasoconstriction in contracting skeletal muscle of humans

Hearon, Christopher M.; Kirby, Brett S.; Luckasen, Gary J.; Larson, Dennis G.; Dinenno, Frank A.

doi:10.1113/jp272829

Cited by 41 publications

(64 citation statements)

References 73 publications

(217 reference statements)

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“…18 Exercise increases cardiac output, and skeletal muscle contraction facilitates circulation in the lower extremities by attenuating sympathetic vasoconstriction to ensure proper blood flow to the muscles. 22,23 Exercises performed with the LEX are designed to increase venous flow in the lower extremities.…”

Section: Introductionmentioning

confidence: 99%

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

Shimizu

Kamada

Sakane

et al. 2017

Journal of Orthopaedic Surgery

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Purpose: Venous thromboembolism prophylaxis is crucial. To facilitate active ankle movement in postoperative and bedridden patients, we developed a novel leg exercise apparatus (LEX). We investigated the effect of the LEX by comparing increases in lower extremity venous flow during different modes of exercise using the LEX. Methods: In eight healthy participants, we measured venous flow volume and velocity in the femoral vein using duplex ultrasonography at 1, 10, 20, and 30 min after completing three modes of 1-min LEX exercises. The exercises involved (1) rapid single motion (ankle dorsi-plantar flexion; 60 cycles/min); (2) slow single motion (30 cycles/min); and (3) slow combined leg motion. Results: Flow volumes after modes 1, 2, and 3 were 1.63-, 1.39-, and 1.53-fold above baseline at 30 min, respectively. Short periods of rapid single motion, with the LEX, improved postexercise lower extremity venous flow volumes at 30 min and mean venous flow velocity at 20 min, compared to slow single motion exercise. Even at slow speeds, combinedmotion improved flow volume compared to single motion. Conclusion: Short periods of rapid single motion exercise, with the LEX, improved postexercise venous flow volumes in the lower extremities at 30 min and mean venous flow velocity at 20 min. These effects were greater than those produced by slow single motion exercises. However, even at slow speeds, combined-motion exercises improved flow volume compared to single motion. Therefore, LEX may prove effective at preventing thromboembolism in postoperative and bedridden patients.

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Section: Introductionmentioning

confidence: 99%

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

Shimizu

Kamada

Sakane

et al. 2017

Journal of Orthopaedic Surgery

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“…), which opposes sympathetic vasoconstriction (Kurjiaka and Segal ; Hearon et al. ), myogenic vasodilation may also be involved. It has been shown in isolated rat arteries (Jasperse et al.…”

Section: Discussionmentioning

confidence: 99%

Difference in the integrated effects of sympathetic vasoconstriction and local vasodilation in human skeletal muscle and skin microvasculature

2019

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We investigated the integration of sympathetic vasoconstriction and local vasodilation in the skeletal muscle and skin microvasculature of humans. In 39 healthy volunteers, we simultaneously measured the blood flow index in the flexor carpi radialis muscle using diffuse correlation spectroscopy and the skin using laser‐Doppler flowmetry. We examined the effects of acute sympathoexcitation induced by forehead cooling on relatively weak and robust vasodilatory responses during postocclusive reactive hyperemia ( PORH ) induced by 70‐sec and 10‐min arterial occlusion in the upper arm. To increase sympathetic tone during PORH , forehead cooling was begun 60 sec before the occlusion release and ended 60 sec after the release. In the 70‐sec occlusion trials, acute sympathoexcitation reduced the peak and duration of vasodilation in both skeletal muscle and skin. The inhibition of vasodilation by sympathoexcitation was blunted in both tissues by the robust vasodilatory stimulation produced by the 10‐min occlusion, and the degree of blunting was greater in skeletal muscle than in skin, especially the initial and peak responses. Sympathoexcitation reduced the peak vasodilation only in skin, while it accelerated the initial vasodilation only in skeletal muscle. However, the decline in vasodilation after the peak was significantly hastened in skeletal muscle, shortening the duration of the vasodilation. We conclude that, in humans, the integration of sympathetic vasoconstriction and local vasodilation has different effects in skeletal muscle and skin and is likely an important contributor to the selective control of perfusion in the microcirculations of different tissues.

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“…; Hearon and Dinenno ; Hearon et al. ), and may impact both local dilatory responses and conducted vasodilation in skeletal muscle. In addition, our data suggest that a low level of α 1 ‐adrenoceptor activation would promote/support the elevated vascular resistance to blood flow typically observed in resting skeletal muscle (Saltin et al.…”

Section: Discussionmentioning

confidence: 99%

Alpha₁-adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries

et al. 2018

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We have systematically investigated how vascular smooth muscle α 1‐adrenoceptor activation impacts endothelium‐mediated vasodilation in isolated, myogenically active, rat cremaster muscle 1A arteries. Cannulated cremaster arteries were pressurized intraluminally to 70 mmHg to induce myogenic tone, and exposed to vasoactive agents via bath superfusion at 34°C. Smooth muscle membrane potential was measured via sharp microelectrode recordings in pressurized, myogenic arteries. The α 1‐adrenergic agonist phenylephrine (25–100 nmol/L) produced further constriction of myogenic arteries, but did not alter the vasorelaxant responses to acetylcholine (0.3 μmol/L), SKA‐31 (an activator of endothelial Ca2+‐dependent K+ channels) (3 μmol/L) or sodium nitroprusside (10 μmol/L). Exposure to 0.25–1 μmol/L phenylephrine or 1 μmol/L norepinephrine generated more robust constrictions, and also enhanced the vasodilations evoked by acetylcholine and SKA‐31, but not by sodium nitroprusside. In contrast, the thromboxane receptor agonist U46619 (250 nmol/L) dampened responses to all three vasodilators. Phenylephrine exposure depolarized myogenic arteries, and mimicking this effect with 4‐aminopyridine (1 mmol/L) was sufficient to augment the SKA‐31‐evoked vasodilation. Inhibition of L‐type Ca2+ channels by 1 μmol/L nifedipine decreased myogenic tone, phenylephrine‐induced constriction and prevented α 1‐adrenergic enhancement of endothelium‐evoked vasodilation; these latter deficits were overcome by exposure to 3 and 10 μmol/L phenylephrine. Mechanistically, augmentation of ACh‐evoked dilation by phenylephrine was dampened by eNOS inhibition and abolished by blockade of endothelial KCa channels. Collectively, these data suggest that increasing α 1‐adrenoceptor activation beyond a threshold level augments endothelium‐evoked vasodilation, likely by triggering transcellular signaling between smooth muscle and the endothelium. Physiologically, this negative feedback process may serve as a “brake” to limit the extent of vasoconstriction in the skeletal microcirculation evoked by the elevated sympathetic tone.

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Endothelium‐dependent vasodilatory signalling modulates α₁‐adrenergic vasoconstriction in contracting skeletal muscle of humans

Abstract: -14 ± 5%). We conclude that stimulation of EDH-like vasodilatation can blunt α -adrenergic vasoconstriction in contracting skeletal muscle of humans.

Cited by 41 publications

References 73 publications

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

Difference in the integrated effects of sympathetic vasoconstriction and local vasodilation in human skeletal muscle and skin microvasculature

Alpha₁-adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries

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Endothelium‐dependent vasodilatory signalling modulates α1‐adrenergic vasoconstriction in contracting skeletal muscle of humans

Abstract: -14 ± 5%). We conclude that stimulation of EDH-like vasodilatation can blunt α -adrenergic vasoconstriction in contracting skeletal muscle of humans.

Cited by 41 publications

References 73 publications

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

Difference in the integrated effects of sympathetic vasoconstriction and local vasodilation in human skeletal muscle and skin microvasculature

Alpha1-adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries

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Endothelium‐dependent vasodilatory signalling modulates α₁‐adrenergic vasoconstriction in contracting skeletal muscle of humans

Alpha₁-adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries