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Current Topics in Pharmacology   Volumes    Volume 8  Issue 1
Cardiovascular pharmacology and possible clinical applications of adenosine, ATP and diadenosine polyphosphates in humans
E. E. M. van Ginneken, J. S. Floras, P. Smits, G. A. Rongen
Pages: 121 - 136
Number of pages: 16
Current Topics in Pharmacology
Volume 8  Issue 1

Copyright © 2004 Research Trends. All rights reserved


This review concentrates on the extracellular actions of adenosine, ATP, and diadenosine polyphosphates in the human cardiovascular system.

Adenosine has important cardiovascular actions: it induces vasodilation, inhibits noradrenaline release from sympathetic nerve endings, inhibits thrombocyte aggregation and has anti-arrhythmic properties. It plays an important role in ischemic preconditioning. Adenosine is generated from enzymatic degradation of ATP. The formation of adenosine is enhanced during ischemia. In humans, adenosine evokes a sympatho-excitatory reflex mediated by chemically sensitive receptors and afferent nerves in the kidney, heart and forearm. This reflex may be active during exercise and ischemia. New therapies are being developed to harness the tissue-protective properties of adenosine against ischemic injury.

ATP is released from aggregating thrombocytes, endothelium, and from sympathetic nerve endings. ATP acts on P2X purinoceptors on vascular smooth muscle cells to induce vasoconstriction. Stimulation of P2Y purinoceptors on endothelial cells induces vasodilation. The mechanism of ATP-induced vasodilation in humans is not elucidated yet. ATP might induce vasospasm at sites of impaired endothelial function and thrombus formation.

Diadenosine polyphosphates are endogenous compounds derived from ATP. They are stored and released from thrombocytes, adrenal medulla, and sympathetic neurons. The functions of the intact molecules as well as their receptors(s) and second messengers are not fully characterized yet. They induce vasodilation as well as vasoconstriction depending of the phosphate chain length. Diadenosine pentaphosphate has received much attention lately, being a possible mediator in the pathogenesis of hypertension, but experimental data are conflicting.

Currently, purine-agonists and antagonists are being developed as therapies against ischemia and other cardiovascular disorders.

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