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.