Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor

Area of Science:

• Vascular Biology
• Endothelial Function
• Pharmacology

Background:

• The endothelium regulates vascular tone, but endothelium-derived vasoconstrictive factors (EDCFs) remain largely unidentified.
• Nitric oxide is a key vasodilator, yet the endogenous vasoconstrictors produced by the endothelium are poorly understood.

Purpose of the Study:

• To identify and characterize novel endothelium-derived vasoconstrictive factors.
• To investigate the role of uridine adenosine tetraphosphate (Up(4)A) in endothelial regulation of vascular tone.

Main Methods:

• Supernatant from mechanically stimulated human endothelial cells was used to elicit vasoconstriction in an isolated perfused rat kidney model.
• Purinoceptor and endothelin receptor blockers were employed to assess the contribution of different receptor pathways.
• Mass spectrometry was utilized to isolate and identify the active vasoconstrictive molecule.

Main Results:

• Mechanical stimulation of endothelial cells released a vasoconstrictive factor.
• Uridine adenosine tetraphosphate (Up(4)A) was identified as a potent vasoconstrictor, acting primarily via P2X1 receptors.
• Up(4)A is released from endothelium upon stimulation with various agents and is present at vasoconstrictive concentrations in healthy subjects.

Conclusions:

• Up(4)A is a novel, potent, nonpeptidic EDCF.
• Up(4)A likely contributes to vascular autoregulation through its release and vasoconstrictive properties.
• The identification of Up(4)A provides new insights into endothelial control of vascular tone.