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GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.

receptors have been shown to have a beneficial life-prolonging role
in heart failure; increased expression or activation of these ATP-
stimulated receptor channels may represent a new therapeutic
approach to the treatment of heart failure (6). Administration of ATP
during sinus rhythm has been suggested as a useful bedside test for
identifying patients with concealed accessory pathway who are prone
to atrioventricular reentrant tachycardia.

ATP release from red blood cells is increased in pathological
conditions such as subarachnoid haemorrhage, largely because
there is widespread blood cell lysis. This leads to transient
constriction of arterioles via P2X receptors and a sustained
constriction of large cerebral vessels, largely through P2Y2 receptors.
The differences in purinergic receptor distribution between
macro- and microvessels in the cerebral circulation are likely to have
important consequences in pathological conditions. In contrast, red
blood cells of humans with primary pulmonary hypertension, fail to
release ATP in response to mechanical deformation. This is likely
to result in the loss of local control of total pulmonary vascular
resistance in the lung.

Magnesium-ATP has been recommended for the treatment of
ischaemia, radiation injury, shock and sepsis for many years.
Treatment of myocardial ischaemia and reperfusion by ATP-MgCl2 is
still recommended, but many reports suggest that adenosine (a
break-down product of ATP) also mediates this effect. Diadenosine
tetraphosphate (AP4A) protects against injuries induced by ischaemia
and 6-hydroxytryptamine in rat brain and has beeen suggested as
a potentially useful target molecule in the therapy of stroke and
Parkinson’s disease. Upregulation of P2X2 and P2X4 receptors in
organotypic cultures of hippocampus, cortex and striatum is
associated with ischaemic cell death and was prevented by P2
receptor antagonists. The protective effect of ATP-MgCl2 in
ischaeamia-reperfusion lung injury appears to require the presence
of leukocytes.

ATP plays a significant cotransmitter role in sympathetic nerves
supplying hypertensive blood vessels. The purinergic component is
increased in SHR (2). ATP is a rapidly acting hypotensive agent that
compares favourably with sodium nitroprusside. ATP-MgCl2 is a safe,

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