Interstitial adenosine triphosphate modulates muscle afferent nerve-mediated pressor reflex

Area of Science:

• Physiology
• Exercise Physiology
• Cardiovascular Physiology

Background:

• Muscle contraction elevates interstitial adenosine triphosphate ([ATP]i), likely from active skeletal muscle release.
• ATP activates purinergic receptors (P2X) on afferent nerve fibers, enhancing cardiovascular responses.
• Understanding ATP release mechanisms and its cardiovascular modulation is crucial.

Purpose of the Study:

• To investigate the mechanisms of ATP release from muscle due to mechanical stimulation.
• To determine how interstitial ATP concentrations modulate the pressor response during muscle contraction.

Main Methods:

• Static contraction of triceps surae muscle induced by electrical stimulation in anesthetized cats.
• Microdialysis used to collect muscle interstitial fluid for ATP concentration measurement (luciferin-luciferase assay).
• Pharmacological agents (gadolinium, glibenclamide, monensin, brefeldin A) used to probe release pathways.

Main Results:

• Muscle contraction significantly increased interstitial ATP concentration ([ATP]i).
• Gadolinium (mechanosensitive channel blocker) reduced ATP release during contraction.
• Inhibitors of exocytosis (glibenclamide, monensin, brefeldin A) did not affect ATP release.
• Interstitial ATP concentration was linearly related to the pressor response.

Conclusions:

• Skeletal muscle ATP release during contraction is primarily mediated by mechanosensitive channels.
• Exocytosis is not a significant pathway for ATP release from contracting muscle.
• Interstitial ATP plays a physiological role in modulating cardiovascular responses to muscle contraction.