CARDIOVASCULAR PHARMACOLOGY OF PURINES

1. This review focuses on the extracellular actions of ATP and adenosi ne, and in particular their role in cardiovascular regulation. 2. ATP serves as a co-transmitter within the sympathetic nervous system, and is also released from endothelium and aggregating thrombocytes. ATP ac ts on P2x purinoceptors on vascular smooth muscle cells to induce vaso constriction. Stimulation of P2y purinoceptors on endothelial cells re leases endothelium-derived relaxing factors and causes vasodilatation, This dual action of ATP may have pathophysiological importance by ind ucing vasospasm at sites of impaired endothelial function and thrombus formation. 3. Adenosine is generated by enzymic degradation of ATP, I ts formation is enhanced during ischaemia. Adenosine inhibits noradren aline release from sympathetic nerve endings, causes vasodilatation vi a endothelium-dependent and endothelium-independent actions, has impor tant anti-arrhythmic properties and prevents deleterious sequelae of i schaemia, In humans, adenosine evokes a sympatho-excitatory reflex med iated by chemically sensitive receptors and afferent nerves in the kid ney, heart and forearm, This reflex may be active during exercise and ischaemia and, because of its potential adverse consequences, it shoul d be considered when developing new therapies to potentiate the anti-i schaemic actions of endogenous adenosine in humans, Adenosine appears to mediate ischaemia-induced pain; a reduced sensitivity to adenosine may underlie silent ischaemia.4. New drugs that interact with adenosin e formation or degradation or with adenosine receptors are under devel opment, These have potential therapeutic application in the treatment of ischaemia and other circulatory disorders.