Diadenosine polyphosphates: postulated mechanisms mediating the cardiac effects

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Purinergic Signaling

Background:

• Diadenosine polyphosphates (Ap(n)A) are endogenous dinucleotides present in human and guinea-pig cardiac tissue.
• They are stored in platelet dense granules and released during platelet activation.
• Ap(n)A encompass compounds like diadenosine triphosphate (Ap3A) to diadenosine hexaphosphate (Ap6A).

Purpose of the Study:

• To review the cardiovascular effects of Ap(n)A, focusing on coronary vasomotor and cardiac electrophysiological actions.
• To elucidate the mechanisms underlying these effects, including receptor interactions and signaling pathways.
• To discuss the potential pro-arrhythmogenic role of Ap(n)A in myocardial ischemia.

Main Methods:

• Literature review of studies investigating Ap(n)A's effects on the cardiovascular system.
• Analysis of research on Ap(n)A receptor interactions, including distinct Ap4A receptors and purinoceptors.
• Examination of studies on the influence of pH, nitric oxide, and prostanoids on Ap(n)A's actions.

Main Results:

• Ap(n)A exhibit varied effects on vascular tone, acting as vasopressors in some tissues and vasodilators in others.
• Evidence suggests interaction with unique Ap4A receptors and potential involvement of purinergic receptors.
• Ap(n)A released from platelets can decrease heart rate, indicating a regulatory role in cardiac function.

Conclusions:

• Ap(n)A are significant regulators of coronary vasomotor tone and myocardial function.
• Their mechanisms involve specific receptors and signaling molecules like nitric oxide and prostanoids.
• Ap(n)A may contribute to cardiac arrhythmias by causing repolarization inhomogeneities during myocardial ischemia.