Nitric oxide-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise

Darren P. Casey, Timothy B Curry, Brad W. Joyner, Michael Joseph Joyner

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Abstract

Casey DP, Curry TB, Wilkins BW, Joyner MJ. Nitric oxidemediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise. J Appl Physiol 110: 687- 694, 2011. First published December 30, 2010; doi:10.1152/japplphysiol.00787.2010.-Hypoxic vasodilation in skeletal muscle at rest is known to include β-adrenergic receptorstimulated nitric oxide (NO) release. We previously reported that the augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes β-adrenergic mechanisms. However, it is unclear whether a β-adrenergic receptor-stimulated NO component exists during hypoxic exercise. We hypothesized that NO-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased exercise intensity during hypoxic exercise. Ten subjects (7 men, 3 women; 23 ± 1 yr) breathed hypoxic gas to titrate arterial O 2 saturation to 80% while remaining normocapnic. Subjects performed two consecutive bouts of incremental rhythmic forearm exercise (10% and 20% of maximum) with local administration (via a brachial artery catheter) of propranolol (β-adrenergic receptor inhibition) alone and with the combination of propranolol and nitric oxide synthase inhibition [NG-monomethyl-L-arginine (L-NMMA)] under normoxic and hypoxic conditions. Forearm blood flow (FBF, ml/min; Doppler ultrasound) and blood pressure [mean arterial pressure (MAP), mmHg; brachial artery catheter] were assessed, and forearm vascular conductance (FVC, ml.min -1.100 mmHg -1) was calculated (FBF/MAP). During propranolol alone, the rise in FVC (δ from normoxic baseline) due to hypoxic exercise was 217 ± 29 and 415 ± 41 ml.min -1cc100 mmHg -1 (10% and 20% of maximum, respectively). Combined propranolol-L-NMMA infusion during hypoxic exercise attenuated δFVC at 20% (352 ± 44 ml.min -1.100 mmHg -1; P < 0.001) but not at 10% (202 ± 28 ml.min -1.100 mmHg -1; P = 0.08) of maximum compared with propranolol alone. These data, when integrated with earlier findings, demonstrate that NO contributes to the compensatory vasodilation during mild and moderate hypoxic exercise; a β-adrenergic receptor-stimulated NO component exists during low-intensity hypoxic exercise. However, the source of the NO becomes less dependent on β-adrenergic mechanisms as exercise intensity increases.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalJournal of Applied Physiology
Volume110
Issue number3
DOIs
StatePublished - Mar 1 2011

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Vasodilation
Adrenergic Receptors
Nitric Oxide
Exercise
Propranolol
omega-N-Methylarginine
Forearm
Adrenergic Agents
Brachial Artery
Arterial Pressure
Skeletal Muscle
Catheters
Doppler Ultrasonography
Nitric Oxide Synthase
Blood Vessels
Gases
Blood Pressure

Keywords

  • Hypoxia
  • Skeletal muscle blood flow

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Nitric oxide-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise",
abstract = "Casey DP, Curry TB, Wilkins BW, Joyner MJ. Nitric oxidemediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise. J Appl Physiol 110: 687- 694, 2011. First published December 30, 2010; doi:10.1152/japplphysiol.00787.2010.-Hypoxic vasodilation in skeletal muscle at rest is known to include β-adrenergic receptorstimulated nitric oxide (NO) release. We previously reported that the augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes β-adrenergic mechanisms. However, it is unclear whether a β-adrenergic receptor-stimulated NO component exists during hypoxic exercise. We hypothesized that NO-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased exercise intensity during hypoxic exercise. Ten subjects (7 men, 3 women; 23 ± 1 yr) breathed hypoxic gas to titrate arterial O 2 saturation to 80{\%} while remaining normocapnic. Subjects performed two consecutive bouts of incremental rhythmic forearm exercise (10{\%} and 20{\%} of maximum) with local administration (via a brachial artery catheter) of propranolol (β-adrenergic receptor inhibition) alone and with the combination of propranolol and nitric oxide synthase inhibition [NG-monomethyl-L-arginine (L-NMMA)] under normoxic and hypoxic conditions. Forearm blood flow (FBF, ml/min; Doppler ultrasound) and blood pressure [mean arterial pressure (MAP), mmHg; brachial artery catheter] were assessed, and forearm vascular conductance (FVC, ml.min -1.100 mmHg -1) was calculated (FBF/MAP). During propranolol alone, the rise in FVC (δ from normoxic baseline) due to hypoxic exercise was 217 ± 29 and 415 ± 41 ml.min -1cc100 mmHg -1 (10{\%} and 20{\%} of maximum, respectively). Combined propranolol-L-NMMA infusion during hypoxic exercise attenuated δFVC at 20{\%} (352 ± 44 ml.min -1.100 mmHg -1; P < 0.001) but not at 10{\%} (202 ± 28 ml.min -1.100 mmHg -1; P = 0.08) of maximum compared with propranolol alone. These data, when integrated with earlier findings, demonstrate that NO contributes to the compensatory vasodilation during mild and moderate hypoxic exercise; a β-adrenergic receptor-stimulated NO component exists during low-intensity hypoxic exercise. However, the source of the NO becomes less dependent on β-adrenergic mechanisms as exercise intensity increases.",
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N2 - Casey DP, Curry TB, Wilkins BW, Joyner MJ. Nitric oxidemediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise. J Appl Physiol 110: 687- 694, 2011. First published December 30, 2010; doi:10.1152/japplphysiol.00787.2010.-Hypoxic vasodilation in skeletal muscle at rest is known to include β-adrenergic receptorstimulated nitric oxide (NO) release. We previously reported that the augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes β-adrenergic mechanisms. However, it is unclear whether a β-adrenergic receptor-stimulated NO component exists during hypoxic exercise. We hypothesized that NO-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased exercise intensity during hypoxic exercise. Ten subjects (7 men, 3 women; 23 ± 1 yr) breathed hypoxic gas to titrate arterial O 2 saturation to 80% while remaining normocapnic. Subjects performed two consecutive bouts of incremental rhythmic forearm exercise (10% and 20% of maximum) with local administration (via a brachial artery catheter) of propranolol (β-adrenergic receptor inhibition) alone and with the combination of propranolol and nitric oxide synthase inhibition [NG-monomethyl-L-arginine (L-NMMA)] under normoxic and hypoxic conditions. Forearm blood flow (FBF, ml/min; Doppler ultrasound) and blood pressure [mean arterial pressure (MAP), mmHg; brachial artery catheter] were assessed, and forearm vascular conductance (FVC, ml.min -1.100 mmHg -1) was calculated (FBF/MAP). During propranolol alone, the rise in FVC (δ from normoxic baseline) due to hypoxic exercise was 217 ± 29 and 415 ± 41 ml.min -1cc100 mmHg -1 (10% and 20% of maximum, respectively). Combined propranolol-L-NMMA infusion during hypoxic exercise attenuated δFVC at 20% (352 ± 44 ml.min -1.100 mmHg -1; P < 0.001) but not at 10% (202 ± 28 ml.min -1.100 mmHg -1; P = 0.08) of maximum compared with propranolol alone. These data, when integrated with earlier findings, demonstrate that NO contributes to the compensatory vasodilation during mild and moderate hypoxic exercise; a β-adrenergic receptor-stimulated NO component exists during low-intensity hypoxic exercise. However, the source of the NO becomes less dependent on β-adrenergic mechanisms as exercise intensity increases.

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