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NO modulates norepinephrine release in human skeletal muscle: implications for neural preconditioning
F Costa1, N J Christensen, G Farley
1Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee 37212-8210, USA.
Summary
This study found that nitric oxide (NO) modulates norepinephrine (NE) release in skeletal muscle during exercise. Inhibiting NO synthesis increased NE levels, suggesting NO
Area of Science:
- Exercise Physiology
- Neuroendocrinology
- Skeletal Muscle Metabolism
Background:
- Norepinephrine (NE) is a key neurotransmitter and hormone involved in the sympathetic nervous system's response to exercise.
- The role of nitric oxide (NO) in modulating NE release within human skeletal muscle during physical exertion remains incompletely understood.
- Investigating the interplay between NO and NE is crucial for understanding muscle function and metabolic regulation during exercise.
Purpose of the Study:
- To quantify muscle interstitial norepinephrine (NE) levels during dynamic exercise in humans.
- To investigate the modulatory effect of nitric oxide (NO) on NE release in skeletal muscle.
- To explore the potential preconditioning effects of exercise and ischemia on NE release.
Main Methods:
- Microdialysis technique was employed to measure interstitial NE concentrations in the forearm.
- Probes were perfused with either saline or N(G)-monomethyl-L-arginine (L-NMMA), a NO synthesis inhibitor.
- Measurements were taken during baseline periods and intense dynamic handgrip exercise, with forearm ischemia performed on a separate occasion.
Main Results:
- Intense dynamic exercise significantly increased muscle interstitial NE levels by 83%.
- Inhibition of NO synthesis with L-NMMA resulted in a 136% greater increase in interstitial NE compared to saline perfusion.
- The exercise-induced increase in NE was attenuated following prior exercise or ischemia, a phenomenon not observed when NO synthesis was inhibited.
Conclusions:
- Nitric oxide (NO) plays a significant role in modulating norepinephrine (NE) release within human skeletal muscle.
- Ischemic exercise leads to elevated muscle interstitial NE, and this effect can be partially mitigated by a NO-mediated preconditioning effect.
- These findings provide novel insights into the neurochemical regulation of skeletal muscle during physical stress.
Keywords:
Non-programmatic