Endogenous ACh tonically stimulates ANP secretion in rat atria

Area of Science:

• Cardiology
• Neuroendocrinology
• Molecular Pharmacology

Background:

• Exogenous acetylcholine (ACh) stimulates atrial natriuretic peptide (ANP) secretion and decreases atrial pulse pressure.
• The role of intrinsic cardiac ACh in ANP regulation was previously unknown.
• Both neuronal and non-neuronal ACh have been identified in cardiac atria.

Purpose of the Study:

• To investigate the hypothesis that endogenously released ACh regulates ANP secretion in an autocrine or paracrine manner.
• To elucidate the signaling pathway involved in intrinsic ACh-mediated ANP secretion.

Main Methods:

• Experiments were conducted using isolated beating rat atria.
• ANP secretion was measured using radioimmunoassay.
• Acetylcholinesterase inhibition, receptor antagonists, and channel blockers were employed to study ACh signaling pathways.

Main Results:

• Physostigmine (acetylcholinesterase inhibitor) increased ANP secretion and decreased atrial dynamics concentration-dependently.
• Inhibition of M2 muscarinic ACh receptors (mAChR) and ACh-activated K+ (KACh+) channels abolished these effects.
• Pertussis toxin treatment and hemicholinium-3 (choline transporter inhibitor) attenuated physostigmine-induced changes, indicating Gi/o protein and ACh synthesis involvement.

Conclusions:

• Endogenously released ACh tonically stimulates ANP secretion from atrial cardiomyocytes.
• The mechanism involves M2 mAChR-Gi/o-KACh+ channel signaling.
• ACh-ANP signaling is suggested to play a role in cardiac physiology and pathophysiology.