Exogenous NO administration and α-adrenergic vasoconstriction in human limbs

Rosenmeier, Jaya B.; Fritzlar, Sandy J.; Dinenno, Frank A.; Joyner, Michael J.

doi:10.1152/japplphysiol.00634.2003

Cited by 42 publications

(41 citation statements)

References 24 publications

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“…In contrast, the effects of tyramine on blood flow during contractions were markedly attenuated, but not eliminated, during exercise intensities that closely matched the blood flow increases caused by the drug infusions. For example, tyramine infusions caused reductions in blood flow of ϳ10 -15% during heavy rhythmic handgrip exercise (81,128,130,385,386,479). These findings are summarized and illustrated in FIGURE 22.…”

Section: B Contraction Blunts Sympathetic Vasoconstrictionmentioning

confidence: 96%

“…In animal models and some human studies, NO has emerged as a mediator of sympatholysis, and there is evidence to both support and reject a role for it (90,128,129,155,467,479). However, administration of exogenous nitrovasodilators does not cause sympatholysis (81,386). To date, exogenous administration of ATP does mimic the sympatholytic effects of contraction on sympathetic vasoconstriction (252,387,388), and this is also one of the primary arguments favoring ATP as a major player in exercise hyperemia.…”

Section: B Contraction Blunts Sympathetic Vasoconstrictionmentioning

confidence: 99%

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Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Joyner

Casey

2015

Physiological Reviews

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581

513

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LJoyner MJ, Casey DP. Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs. Physiol Rev 95: 549 -601, 2015; doi:10.1152/physrev.00035.2013.-This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans.

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Section: B Contraction Blunts Sympathetic Vasoconstrictionmentioning

confidence: 96%

Section: B Contraction Blunts Sympathetic Vasoconstrictionmentioning

confidence: 99%

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Joyner

Casey

2015

Physiological Reviews

Self Cite

581

513

View full text Add to dashboard Cite

show abstract

“…At present, neither adenosine nor prostaglandins appear to be obligatory for functional sympatholysis (20,34,69,90,93). In contrast, a study in humans has implicated local tissue hypoxia as an important factor in the attenuated vasoconstrictor response to SNA in exercising muscle (34).…”

Section: Mechanisms Underlying Functional Sympatholysismentioning

confidence: 95%

Neural control of muscle blood flow during exercise

Thomas¹,

Segal

2004

Journal of Applied Physiology

220

174

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.-Activation of skeletal muscle fibers by somatic nerves results in vasodilation and functional hyperemia. Sympathetic nerve activity is integral to vasoconstriction and the maintenance of arterial blood pressure. Thus the interaction between somatic and sympathetic neuroeffector pathways underlies blood flow control to skeletal muscle during exercise. Muscle blood flow increases in proportion to the intensity of activity despite concomitant increases in sympathetic neural discharge to the active muscles, indicating a reduced responsiveness to sympathetic activation. However, increased sympathetic nerve activity can restrict blood flow to active muscles to maintain arterial blood pressure. In this brief review, we highlight recent advances in our understanding of the neural control of the circulation in exercising muscle by focusing on two main topics: 1) the role of motor unit recruitment and muscle fiber activation in generating vasodilator signals and 2) the nature of interaction between sympathetic vasoconstriction and functional vasodilation that occurs throughout the resistance network. Understanding how these control systems interact to govern muscle blood flow during exercise leads to a clear set of specific aims for future research.

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“…Consequently, the increase in exercise hyperemia with PDE5 inhibition in older subjects (26) could also reflect that a lower cGMP level during exercise was, at least in part, related to a diminished NO bioavailability. As opposed to the reports on the vascular effects of ATP, consistent evidence has been provided to support that NO is neither sufficient nor essential for functional sympatholysis in humans (9,31,33,41). Consequently, an NO-mediated increase in local vasodilation in the contracting leg muscles would, therefore, be expected to be independent of an improved ability for functional sympatholysis.…”

mentioning

confidence: 88%

“…As the vasodilator effect of NO is mediated via cGMP (35), one mechanism underlying the increase in exercise hyperemia with PDE5 inhibition in older subjects (26) could be an improved cGMP signaling, which would serve to potentiate the effect of NO and thereby compensate for a diminished NO bioavailability. Notably, pharmacological inhibition of NO synthesis does not impact the ability of contracting forearm muscles to blunt vasoconstrictor responses to tyramine as well as ␣ 1 -and ␣ 2 -adrenoceptor agonists (7,9) and infusion of SNP also fails to blunt vasoconstrictor responses to tyramine and ␣ 1 -and ␣ 2 -adrenoceptor agonists in the forearm (33,41). Furthermore, infusion of ascorbic acid increases NO-mediated vasodilation in the exercising forearm of older individuals without improving functional sympatholysis (31).…”

Section: Effect Of Pde5 Inhibition On Plasma [Atp] and Functional Symmentioning

confidence: 99%

Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans

Nyberg

Piil

Egelund

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Nyberg M, Piil P, Egelund J, Sprague RS, Mortensen SP, Hellsten Y. Effect of PDE5 inhibition on the modulation of sympathetic ␣-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans. Am J Physiol Heart Circ Physiol 309: H1867-H1875, 2015. First published October 2, 2015; doi:10.1152/ajpheart.00653.2015.-Aging is associated with an altered regulation of blood flow to contracting skeletal muscle; however, the precise mechanisms remain unclear. We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not young human subjects. Here we examined whether this effect of PDE5 inhibition was related to an improved ability to blunt ␣-adrenergic vasoconstriction (functional sympatholysis) and/or improved efficacy of local vasodilator pathways. A group of young (23 Ϯ 1 yr) and a group of older (72 Ϯ 1 yr) male subjects performed kneeextensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. During both conditions, exercise was performed without and with arterial tyramine infusion to evoke endogenous norepinephrine release and consequently stimulation of ␣1-and ␣2-adrenergic receptors. The level of the sympatholytic compound ATP was measured in venous plasma by use of the microdialysis technique. Sildenafil increased (P Ͻ 0.05) vascular conductance during exercise in the older group, but tyramine infusion reduced (P Ͻ 0.05) this effect by 38 Ϯ 9%. Similarly, tyramine reduced (P Ͻ 0.05) the vasodilation induced by arterial infusion of a nitric oxide (NO) donor by 54 Ϯ 9% in the older group, and this effect was not altered by sildenafil. Venous plasma [ATP] did not change with PDE5 inhibition in the older subjects during exercise. Collectively, PDE5 inhibition in older humans was not associated with an improved ability for functional sympatholysis. An improved efficacy of the NO system may be one mechanism underlying the effect of PDE5 inhibition on exercise hyperemia in aging.sildenafil; exercise; ATP; nitric oxide; cGMP NEW & NOTEWORTHY We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not young human subjects. Here we demonstrate that this effect of PDE5 inhibition on exercise hyperemia was related to an improved efficacy of local nonsympatholytic vasodilator pathways.CONTRACTILE ACTIVITY markedly increases the O 2 demand in skeletal muscle, thus requiring an increase in blood flow and O 2 delivery to the tissue. This increase in blood flow to the exercising muscle is the result of a local attenuation of the vasoconstrictor effect of sympathetic nervous activity, termed functional sympatholysis, and vasodilation induced by local vasoactive mechanisms (6,15). Since the first report on the hemodynamic response to exercise in older individuals in 1974 (42), evidence has accumulated for an insufficient blood flow to contracting skeletal m...

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Exogenous NO administration and α-adrenergic vasoconstriction in human limbs

Cited by 42 publications

References 24 publications

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Neural control of muscle blood flow during exercise

Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans

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