Vasoconstriction in active skeletal muscles: a potential role for P2X  purinergic receptors?

Buckwalter, John B.; Hamann, Jason J.; Clifford, Philip S.

doi:10.1152/japplphysiol.00173.2003

Cited by 28 publications

(34 citation statements)

References 42 publications

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“…A major strength of the present experimental approach is the ability to study basic physiological mechanisms of vascular control in conscious dynamically exercising animals by delivering selective agonists and antagonists to a discrete vascular bed without altering blood pressure or blood flow in other vascular beds. The findings of the present study in young and old dogs were similar in several respects to previous studies from our laboratory in young mongrel dogs (5,6,8,9). Consistent with those studies, local and systemic hemodynamic variables increased in a manner dependent on exercise intensity and evidence of tonic adrenergic and nonadrenergic sympathetic vasoconstriction was observed at rest and during exercise.…”

Section: Discussionsupporting

confidence: 92%

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

DeLorey

Buckwalter

Mittelstadt

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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.2010.-We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young (n ϭ 6; 22 Ϯ 1 mo; means Ϯ SE) and old (n ϭ 6; 118 Ϯ 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P2x) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 Ϯ 34%; Old: 98 Ϯ 19%) and during exercise at 2.5 mph (Young: 80 Ϯ 10%; Old: 58 Ϯ 12%) and 4 mph and 2.5% grade (Young: 57 Ϯ 5%; Old: 26 Ϯ 4%). Rauwolscine caused similar (P Ͼ 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 Ϯ 25%; Old: 64 Ϯ 22%) and at 2.5 mph (Young: 86 Ϯ 13%; Old: 60 Ϯ 7%) and 4 mph with 2.5% grade (Young: 61 Ϯ 5%; Old: 43 Ϯ 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-D-arginine amide (BIBP) caused a smaller increase (P Ͻ 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 Ϯ 44%; Old: 91 Ϯ 22%), whereas similar increases (P Ͼ 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 Ϯ 16%; Old: 50 Ϯ 12%) and 4 mph and 2.5% grade (Young: 45 Ϯ 10%; Old: 25 Ϯ 7%). Pyridoxal-phosphate-6-azophenyl-2=-4=-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 Ϯ 14%; Old: 191 Ϯ 58%), whereas similar increases were observed at 2.5 mph (Young: 47 Ϯ 18%; Old: 31 Ϯ 11%) and 4 mph with 2.5% grade (Young: 26 Ϯ 13%; Old: Ϫ18 Ϯ 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P2x receptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.aging; sympathetic vasoconstriction; skeletal muscle; exercise AGING IS ASSOCIATED WITH A decline in aerobic capacity (12)(13)(14). An inability to augment cardiac output during exercise has been functionally linked to the reduced exercise tolerance with aging (1, 23, 36, 53). A blunted skeletal muscle blood flow response to dynamic exercise has also been reported in older humans and animals (1,33,37,47,48,50). However, other studies have documented preserved skeletal muscle blood flow during exercise in aged humans (38,40,44,49). Thus, the effect of aging on the control of skeletal muscle blood flow appears to be an unresolved issue in the scientific literature.The observation of elevated efferent muscle sympathetic nerve activity in older adults at rest (16, 43) has led to the notio...

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Section: Discussionsupporting

confidence: 92%

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

DeLorey

Buckwalter

Mittelstadt

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We hypothesized that the mechanism of this attenuation may be related to a change in the chemical environment during exercise. Heavy exercise can result in decreased pH, and, therefore, the current study provides a plausible mechanism for these observations (4,5,13,21).…”

Section: Discussionmentioning

confidence: 55%

“…The physiological significance of these findings is that they provide a potential mechanism to explain observations regarding skeletal muscle vasculature during exercise (4). Recently, our lab demonstrated (5) that P2X receptors mediate tonic vasoconstriction in exercising skeletal muscle.…”

Section: Discussionmentioning

confidence: 80%

“…In skeletal muscle, vasoconstriction is predominantly mediated by norepinephrine release from adrenergic neurons, which stimulates both ␣ 1 -and ␣ 2 -postjunctional receptors on vascular smooth muscle. However, there is growing evidence that P2X purinergic receptors on vascular smooth muscle play an important role in vasoconstriction at rest and during exercise (4,5). These receptors are activated by ATP, which is a cotransmitter released with norepinephrine from the sympathetic nerves (7,9,11,19).…”

mentioning

confidence: 99%

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Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries

Kluess

Buckwalter

Hamann

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries. Am J Physiol Heart Circ Physiol 288: H129 -H132, 2005. First published September 16, 2004; doi:10.1152/ ajpheart.00574.2004.-Vasoconstriction via ␣2-receptors is known to be sensitive to acidic pH, but little is known about the pH sensitivity of P2X receptors. ATP is a cotransmitter released with norepinephrine from the sympathetic nerves and causes vasoconstriction via P2X purinergic receptors on vascular smooth muscle. We hypothesized that reductions in pH would attenuate P2X-mediated vasoconstriction in iliofemoral artery rings. Twenty-five rats were killed, and the iliac and femoral arteries were dissected out and placed in modified Krebs-Henseleit buffer. The arteries were cut into 2-mm sections and mounted in an organ tissue bath. Tension (g) was measured during a potassium chloride and norepinephrine challenge (maximal tension). The arteries were then exposed to ␣,␤-methylene ATP (10 Ϫ7 -10 Ϫ3 M; n ϭ 13) or phenylephrine (10 Ϫ7 -10 Ϫ4 M; n ϭ 6) with a tissue bath pH of 7.8, 7.4, and 7.0. Dose-response curves were fit with nonlinear regression analysis to calculate the EC50 and slope. The peak tension with ␣,␤-methylene ATP was lower during pH 7.0 (1.37 Ϯ 0.09 g) compared with pH 7.8 (1.90 Ϯ 0.12 g). EC50 was highest with pH 7.4 (Ϫ5.38 Ϯ 0.18 log M ␣,␤-methylene ATP) and lowest with pH 7.0 (Ϫ4.9 Ϯ 0.10 log M ␣,␤-methylene ATP). The slopes of the doseresponse curves were not different. Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) abolished contraction caused by the addition of ␣,␤-methylene ATP (n ϭ 6). There was no effect of pH on phenylephrine dose-response curves. These data indicate that the vasoconstrictor response to ␣,␤-methylene ATP is sensitive to pH and that lower pH attenuates the response of P2X purinergic receptors. hydrogen ion; vascular smooth muscle; pH PURINERGIC RECEPTORS ARE PRESENT in most organ systems in the body, and there is accumulating evidence that they play an important role in vascular control in the tail, ear, mesenteric, and skeletal muscle vascular beds (3-5, 7, 20). In skeletal muscle, vasoconstriction is predominantly mediated by norepinephrine release from adrenergic neurons, which stimulates both ␣ 1 -and ␣ 2 -postjunctional receptors on vascular smooth muscle. However, there is growing evidence that P2X purinergic receptors on vascular smooth muscle play an important role in vasoconstriction at rest and during exercise (4, 5). These receptors are activated by ATP, which is a cotransmitter released with norepinephrine from the sympathetic nerves (7,9,11,19).In the skeletal muscle vascular bed, physiological conditions (e.g., exercise) and pathological conditions (e.g., peripheral arterial insufficiency) cause a decrease in pH that may influence the regulation of vascular control (2, 13, 21). The pH sensitivity of adrenergic receptors in conduit arteries varies widely across vascular beds, but data suggest that the sensitivity of ␣ 2 -receptors is decreased with acidic pH (12,15,1...

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“…In addition to norepinephrine, sympathetic nerves also release ATP, which causes vasoconstriction by activating P 2X purinoreceptors. A recent study in dogs suggests that P 2X purinoreceptor vasoconstriction also is attenuated in exercising muscle (7). Whether similar mechanisms modulate P 2X purinoreceptor and ␣-adrenoreceptor vasoconstriction in active muscle remains to be determined.…”

Section: Mechanisms Underlying Functional Sympatholysismentioning

confidence: 99%

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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Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

Cited by 28 publications

References 42 publications

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries

Neural control of muscle blood flow during exercise

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