Extracellular ATP signaling in equine digital blood vessels.

This study investigates how ATP (adenosine triphosphate) signaling functions in blood vessels of horse feet, particularly focusing on the role of specific ATP-activated receptors called P2 receptors in managing blood flow and temperature. The researchers found that different subtypes of P2X receptors, dependent on the type of vessel, mediate the constriction process in these vessels, which could have implications for understanding and managing equine laminitis, a painful hoof condition.

Study Design and Procedure

• Several experiments were performed with equine digital arteries (EDA) and veins (EDV), sections of an animal’s vasculature system that are close to the surface and are involved in thermoregulation and potential foot injuries related to inconsistent blood flow.
• In isometric tension studies, electric field stimulation (EFS) and concentration-response curves were measured under low tone conditions. EFS is a method by which researchers stimulate an action in cells, here to inspect how these responses occur in horse blood vessels.
• The researchers also performed tests to locate and identify specific P2X and P2Y receptor subtypes through a technique called immunofluorescent localization. These receptors respond to ATP and are crucial in managing vessel constriction and dilation.

Key Findings

• EFS-triggered constriction was completely stopped by a poison called tetrodotoxin.
• The constriction induced by EFS wasn’t affected by endothelium denudation, suggesting that it’s not influenced by the vessel inner layer.
• Drugs like phentolamine and suramin (P2 receptor antagonists), reduced EFS-induced constriction in both EDA and EDV, signalling the role of P2 receptors in these responses.
• Application of external methoxamine (an α-adrenergic agonist) and ATP reproduced the EFS-induced constriction in EDA and EDV, confirming noradrenaline and ATP as co-transmitters in these nerves.
• Immunostaining enabled the identification of P2X1, P2X2 and P2X3 receptor subtypes in EDA and EDV smooth muscle, and P2X1 and P2X7 in the adventitia (outer layer), indicating the involvement of different P2X subunits in different sections of the vessels.

Conclusions and Further Implications

• P2X receptors mediate the vasoconstriction in EDA and EDV, although different P2X subunits are involved in different blood vessels.
• The physiological implications of these findings relate to thermoregulatory functions and to a greater understanding of equine laminitis, a disease affecting horse feet which may be associated with blood flow disturbances.