NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex

Hanjun Wang, Yan Xia Pan, Wei Zhong Wang, Irving H Zucker, Wei Wang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Muscle metabolic by-products during exercise, such as K+, lactic acid, ATP, H+, and phosphate, are well established to be involved in the reflex cardiovascular response to static muscle contraction. However, the role of muscle reactive oxygen species (ROS), a metabolic by-product during muscle contraction, in the exercise pressor reflex (EPR) has not been investigated in detail. In the present study, we evaluated the role of muscle ROS in the EPR in a decerebrate rat model. We hypothesized that muscle NADPH oxidase-derived ROS contributes to sensitization of the EPR. Thus the rise in blood pressure and heart rate in response to a 30-s static contraction induced by electrical stimulation of L4/L5 ventral roots was compared before and after hindlimb arterial infusion of the redox agents: diethyldithiocarbamate, a superoxide dismutase inhibitor; the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (tempol); the free radical scavenger dimethylthiourea; a NADPH oxidase inhibitor, apocynin; and a xanthine oxidase inhibitor, allopurinol. The EPR-induced pressor response was augmented after treatment with diethyldithiocarbamate and was attenuated after treatment with tempol, dimethylthiourea, and apocynin. Treatment with allopurinol did not affect the EPR function. None of the drug's affected the EPR heart rate response. In addition, neither the pressor response to electrical stimulation of the central end of dorsal roots, nor femoral blood flow was affected by any treatment. These data suggest that NADPH oxidase-derived muscle ROS plays an excitatory role in the EPR control of blood pressure.

Original languageEnglish (US)
Pages (from-to)450-459
Number of pages10
JournalJournal of Applied Physiology
Volume107
Issue number2
DOIs
StatePublished - Aug 1 2009

Fingerprint

NADPH Oxidase
Reflex
Reactive Oxygen Species
Skeletal Muscle
Muscles
Ditiocarb
Allopurinol
Spinal Nerve Roots
Muscle Contraction
Electric Stimulation
Superoxide Dismutase
Heart Rate
Blood Pressure
Free Radical Scavengers
Xanthine Oxidase
Therapeutics
Hindlimb
Thigh
Oxidation-Reduction
Lactic Acid

Keywords

  • Blood pressure
  • Decerebration
  • Static contraction
  • Sympathetic outflow

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex. / Wang, Hanjun; Pan, Yan Xia; Wang, Wei Zhong; Zucker, Irving H; Wang, Wei.

In: Journal of Applied Physiology, Vol. 107, No. 2, 01.08.2009, p. 450-459.

Research output: Contribution to journalArticle

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abstract = "Muscle metabolic by-products during exercise, such as K+, lactic acid, ATP, H+, and phosphate, are well established to be involved in the reflex cardiovascular response to static muscle contraction. However, the role of muscle reactive oxygen species (ROS), a metabolic by-product during muscle contraction, in the exercise pressor reflex (EPR) has not been investigated in detail. In the present study, we evaluated the role of muscle ROS in the EPR in a decerebrate rat model. We hypothesized that muscle NADPH oxidase-derived ROS contributes to sensitization of the EPR. Thus the rise in blood pressure and heart rate in response to a 30-s static contraction induced by electrical stimulation of L4/L5 ventral roots was compared before and after hindlimb arterial infusion of the redox agents: diethyldithiocarbamate, a superoxide dismutase inhibitor; the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (tempol); the free radical scavenger dimethylthiourea; a NADPH oxidase inhibitor, apocynin; and a xanthine oxidase inhibitor, allopurinol. The EPR-induced pressor response was augmented after treatment with diethyldithiocarbamate and was attenuated after treatment with tempol, dimethylthiourea, and apocynin. Treatment with allopurinol did not affect the EPR function. None of the drug's affected the EPR heart rate response. In addition, neither the pressor response to electrical stimulation of the central end of dorsal roots, nor femoral blood flow was affected by any treatment. These data suggest that NADPH oxidase-derived muscle ROS plays an excitatory role in the EPR control of blood pressure.",
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