The effects of diadenosine polyphosphates on the cardiovascular system

Diadenosine polyphosphates are members of a group of dinucleoside polyphosphates that are ubiquitous, naturally occurring molecules. They form a recently identified class of compounds derived from ATP and consist of two adenosine molecules bridged by up to six phosphate groups. These compounds are stored in high concentrations in platelet dense granules and are released when platelets become activated. Some of the compounds promote platelet aggregation, while others are inhibitory. Possible roles as neurotransmitters, extracellular signalling molecules or 'alarmones' secreted by cells in response to physiologically stressful stimuli have been postulated. Recent studies suggest a role for these compounds in atrial and synaptic neurotransmission. Studies using isolated mesenteric arteries indicate an important role of phosphate chain length in determining whether diadenosine polyphosphates produce vasodilatation or vasoconstriction, but in the coronary circulation, diadenosine polyphosphates generally produce vasodilatation via mechanisms thought to involve release of NO or prostacyclin (PGI(2)). They produce cardiac electrophysiological effects by altering ventricular refractoriness at submicromolar concentrations and reduce heart rate. Mechanisms involving K-ATP channels have been proposed in addition to the involvement of P1- and P2-purinergic receptors and the specific diadenosine polyphosphate receptor identified on isolated cardiac myocytes. Clinical evidence suggests a role for diadenosine polyphosphates in hypertensive patients and those with the Chediak-Higashi syndrome. This review outlines the effects of these compounds on the cardiovascular system and considers their potential involvement in mediating the pathophysiological effects associated with platelet activation during myocardial ischaemia. (C) 1999 Elsevier Science B.V. All rights reserved.