Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Cardiac Electrophysiology

Background:

• Adenosine A(2a)-receptor activation is known to enhance cardiomyocyte shortening.
• The specific impact of A(2a)-receptor activation on the contractile performance of intact hearts requires further elucidation.

Purpose of the Study:

• To investigate the effect of adenosine A(2a)-receptor activation on the contractile performance of isolated rat hearts.
• To determine if these effects are mediated through A(2a) receptors and are independent of beta(1)-adrenergic receptor activation or coronary flow changes.

Main Methods:

• Isolated rat hearts were perfused under constant-pressure or constant-flow conditions.
• Left ventricular pressure (LVP) and the maximal rate of LVP development (+dP/dt(max)) were recorded.
• Pharmacological agents including A(2a)-receptor agonists and antagonists, beta(1)-adrenergic antagonist atenolol, and A(1)-receptor antagonist dipropylcyclopentylxanthine were used.

Main Results:

• Adenosine administration caused concentration-dependent increases in LVP and +dP/dt(max) in isolated rat hearts.
• These positive inotropic effects were specifically blocked by A(2a)-receptor antagonists (chlorostyryl-caffeine and ZM-241385).
• The effects were not influenced by the beta(1)-adrenergic antagonist atenolol or changes in coronary flow, and were potentiated by A(1)-receptor antagonists.

Conclusions:

• Adenosine enhances contractile performance in the intact heart primarily through the activation of A(2a) receptors.
• This positive inotropic effect is independent of beta(1)-adrenergic receptor signaling.
• The observed improvements in cardiac contractility are not mediated by alterations in coronary blood flow.