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(Circulation Research. 2008;103:1056.)
© 2008 American Heart Association, Inc.

Editorials

Endothelium-Derived Vasoconstriction by Purines and Pyrimidines

Geoffrey Burnstock

From the Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, United Kingdom.

Correspondence to Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill St, London, NW3 2PF, United Kingdom. E-mail g.burnstock@ucl.ac.uk

See related article, pages 1100–1108

Key Words: endothelium • kidney • P2X₁ receptors • purinergic • vasoconstriction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The article by Tölle et al¹ claims to show for the first time that adenosine 5'-tetraphosphate (AP4) is released on mechanical stimulation from human microvascular endothelial cells in the perfused rat kidney and, further, that AP4 is the most potent mediator of vascular smooth muscle constriction via P2X₁ receptors or, indeed, via noradrenaline.

It is well established that ATP and UTP released from endothelial cells in response to sheer stress produced by changes in blood flow act largely on P2Y receptor subtypes (but also some P2X receptor subtypes) on endothelial cells to release nitric oxide (NO), leading to vasodilatation (Figure).^2–5 Endothelium-derived contracting factors have been identified, notably endothelin-1, prostaglandin H₂, thromboxane A₂, and superoxide anions.^6,7 Tölle et al¹ present compelling evidence for the release of AP4 from endothelial cells in response to mechanical stimulation, which then acts as a vasoconstrictor of the smooth muscle of microvessels in the kidney via P2X₁ receptors. The presence of P2X₁ receptors on vascular smooth muscle is well established, and they have been shown to respond to ATP released as a cotransmitter with noradrenaline from perivascular sympathetic vasoconstrictor nerves.⁸ However, P2X₁ receptors have also been described on endothelial cells of human internal mammary and radial arteries and saphenous vein.⁹ Occupation of endothelial P2X₁ receptors in rat mesenteric arteries resulted in a small vasoconstriction, followed by a profound and sustained endothelium-dependent vasodilatation, although not via NO.¹⁰ In P2X₁ knockout mice, the vasoconstrictor response to ATP released by nerve stimulation is abolished.¹¹ However, . . . [Full Text of this Article]

Related Article:

Adenosine 5'-Tetraphosphate Is a Highly Potent Purinergic Endothelium-Derived Vasoconstrictor

Markus Tölle, Vera Jankowski, Mirjam Schuchardt, Annette Wiedon, Tao Huang, Franziska Hub, Joanna Kowalska, Jacek Jemielity, Andrzej Guranowski, Christoph Loddenkemper, Walter Zidek, Joachim Jankowski, and Markus van der Giet
Circ. Res. 2008 103: 1100-1108. [Abstract] [Full Text] [PDF]