The effects of diadenosine polyphosphates on the cardiovascular system

Diadenosine polyphosphates are members of a group of dinucleoside polyphosp hates that are ubiquitous, naturally occurring molecules. They form a recen tly identified class of compounds derived from ATP and consist of two adeno sine molecules bridged by up to six phosphate groups. These compounds are s tored in high concentrations in platelet dense granules and are released wh en platelets become activated. Some of the compounds promote platelet aggre gation, while others are inhibitory. Possible roles as neurotransmitters, e xtracellular signalling molecules or 'alarmones' secreted by cells in respo nse to physiologically stressful stimuli have been postulated. Recent studi es suggest a role for these compounds in atrial and synaptic neurotransmiss ion. 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 circulatio n, diadenosine polyphosphates generally produce vasodilatation via mechanis ms 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 involvin g K-ATP channels have been proposed in addition to the involvement of P1- a nd P2-purinergic receptors and the specific diadenosine polyphosphate recep tor identified on isolated cardiac myocytes. Clinical evidence suggests a r ole for diadenosine polyphosphates in hypertensive patients and those with the Chediak-Higashi syndrome. This review outlines the effects of these com pounds on the cardiovascular system and considers their potential involveme nt in mediating the pathophysiological effects associated with platelet act ivation during myocardial ischaemia. (C) 1999 Elsevier Science B.V. All rig hts reserved.