Positive inotropic effect in the heart produced by acetylcholine

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Molecular Cardiology

Background:

• Muscarinic receptor activation in cardiac tissue typically elicits negative chronotropic and inotropic responses.
• The precise effects of acetylcholine (ACh) on cardiac contractility and hemodynamics require further elucidation, especially in human tissues.

Purpose of the Study:

• To investigate the inotropic and hemodynamic effects of acetylcholine (ACh) on human atrial muscle and isolated working rat hearts.
• To explore the potential signaling pathways, such as inositol phosphates, involved in ACh-mediated cardiac responses.

Main Methods:

• Experiments were conducted using human right atrial strips and isolated working rat hearts.
• Acetylcholine (ACh) was applied in varying concentrations (10(-7) - 10(-4) M) to assess dose-dependent effects.
• Measurements included contractility (inotropic state), coronary flow, and cardiodynamic indices; atropine was used as an antagonist, and [3H]phosphoinositide breakdown was measured in rat ventricular strips.

Main Results:

• Acetylcholine (ACh) induced a tri-phasic (positive-negative-positive) inotropic effect in approximately 40% of human atrial strips, with positive effects also observed upon washout.
• In rat hearts, ACh initially decreased coronary flow and cardiac function, but potentiated cardiodynamic indices when adenosine was co-administered.
• Cholinergic stimulation increased inositol phosphate formation in rat ventricular strips, suggesting a role for IP3.

Conclusions:

• Cholinergic muscarinic stimulation can paradoxically produce positive inotropic effects in both human and rat cardiac muscle.
• The vasodilator adenosine may unmask or enhance ACh-induced positive inotropic effects in the working rat heart.
• Inositol trisphosphate (IP3) is suggested as a potential mediator of these positive inotropic responses to acetylcholine.