Purinergic and Pyriminergic Activation of the Endothelium in Regulation of Tissue Perfusion - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 9

1.8.6 Pulmonary Hypertension
Erythrocyte release of ATP regulates pulmonary resistance [63], and patients with
pulmonary hypertension has impaired release of ATP from red blood cells [64].
Endothelium-dependent relaxation to ATP has been demonstrated in human pul-
monary arteries [31]. Infusions of ATP-MgCl 2 have been claimed to be clinically
useful in the treatment of children with pulmonary hypertension [8]. The endothe-
lium derived vasoconstrictive factor UP 4 A is a potent vasoconstrictor in pulmonary
arteries and may have a similar effect as endothelin in pulmonary hypertension [32].
1.8.7 Congestive Heart Failure
Congestive heart failure is accompanied by impaired peripheral blood flow and
endothelial dysfunction with decreased release of NO. In a model of non-
atherosclerotic congestive heart failure there was a minor decrease in P2Y-mediated
total dilatation and a marked down-regulation of the NO-mediated dilatation, while
the EDHF-dilatation was up-regulated. Increased EDHF-activity in CHF may rep-
resent a compensatory response to decreased NO-activity to preserve endothelial
function and tissue perfusion [42].
1.9 Conclusion
Purines and pyrimidines are released into the vascular lumen from red blood cells
and endothelial cells in situations when there is a need for increased tissue perfusion.
They activate several P2-receptors on endothelial cells stimulating vasodilatation
through release of NO and EDHF. A mechanism has been demonstrated of retro-
grade spreading of the dilatation to the supplying artery, thereby enabling improved
tissue perfusion. This system is ubiquitous and could be important for normal
physiology and cardiovascular disease.
References
1. Bar I, Guns PJ, Metallo J, Cammarata D, Wilkin F, Boeynams JM, Bult H, Robaye B. (2008)
Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular
smooth muscle cells. Mol Pharmacol 74:777-84.
2. Bergfeld GR, Forrester T. (1992) Release of ATP from human erythrocytes in response to a
brief period of hypoxia and hypercapnia. Cardiovasc Res 26:40-7.
3. Bodin P, Bailey D, Burnstock G. (1991) Increased flow-induced ATP release from isolated
vascular endothelial cells but not smooth muscle cells. Br J Pharmacol 103:1203-5.
4. Bodin P, Burnstock G. (1996) ATP-stimulated release of ATP by human endothelial cells.
J Cardiovasc Pharmacol 27:872-5.
5. Boehm S, Huck S. (1997) Receptors controlling transmitter release from sympathetic neurons
in vitro. Progress in Neurobiology 51:225-42.