Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

Michael Nyberg, Peter Piil, Jon Egelund, Randy S Sprague, Stefan P Mortensen, Ylva Hellsten

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Resumé

Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6-9%) and leg O2 uptake (10-12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age.

OriginalsprogEngelsk
Artikelnummere12508
TidsskriftPhysiological Reports
Vol/bind3
Udgave nummer8
Antal sider12
ISSN2051-817X
DOI
StatusUdgivet - 2015

Fingeraftryk

Skeletal Muscle
Oxygen
Leg
Perfusion
Vasodilation
Smooth Muscle
Knee
Muscles
Enzymes
Sildenafil Citrate

Citer dette

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abstract = "Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6-9{\%}) and leg O2 uptake (10-12{\%}) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age.",
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Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans. / Nyberg, Michael; Piil, Peter; Egelund, Jon; Sprague, Randy S; Mortensen, Stefan P; Hellsten, Ylva.

I: Physiological Reports, Bind 3, Nr. 8, e12508, 2015.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

AU - Nyberg, Michael

AU - Piil, Peter

AU - Egelund, Jon

AU - Sprague, Randy S

AU - Mortensen, Stefan P

AU - Hellsten, Ylva

N1 - © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

PY - 2015

Y1 - 2015

N2 - Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6-9%) and leg O2 uptake (10-12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age.

AB - Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6-9%) and leg O2 uptake (10-12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age.

U2 - 10.14814/phy2.12508

DO - 10.14814/phy2.12508

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VL - 3

JO - Physiological Reports

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SN - 2051-817X

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ER -