Uridine adenosine tetraphosphate (Up4A) has been identified as an endothelium-derived contracting factor, which acts through purinergic P2X and P2Y receptors. Since the coronary vascular actions of Up4A are unknown, we investigated the vasoactive profile of Up4A in coronary microvessels, and studied the involvement of purinergic receptor subtypes. Studies were performed in isolated porcine coronary small arteries (diameter ∼ 250 μm), with and without endothelial denudation, mounted on a Mulvany wire myograph. Purinergic receptor expression was assessed by real-time PCR. Up4A (10-9-10 -5 M) failed to induce contraction at basal tone, but produced concentration-dependent vasorelaxation in precontracted microvessels. Up4A was slightly less potent than adenosine, ATP, and ADP in producing vasorelaxation, but significantly more potent than UTP and UDP. mRNA expression of P2X 4, P2Y1, P2Y2, P2Y4, P2Y6 and A2A, but not P2X1, receptors was observed. Up4A-induced vasodilation was unaffected by non-selective P2 receptor antagonist PPADS, P2X1 antagonist MRS2159, P2Y1 antagonist MRS2179 and P2Y6 antagonist MRS2578, but was markedly attenuated by non-selective P1 receptor antagonist 8PT and A2A antagonist SCH58261. Up4A-induced vasodilation was not affected by ectonucleotidase inhibitor ARL67156, suggesting that A2A stimulation was not the result of Up4A breakdown to adenosine. Up4A-induced vasodilation was blunted in denuded vessels; additional A2A receptor blockade further attenuated Up4A-induced vasodilation, suggesting that A2A receptor-mediated vasodilation is only partly endothelium-dependent. In conclusion, Up4A exerts a vasodilator rather than a vasoconstrictor influence in coronary microvessels, which is mediated via A2A receptors and is partly endothelium-dependent.

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doi.org/10.1016/j.phrs.2012.09.011, hdl.handle.net/1765/69718
Pharmacological Research
Department of Cardio-Thoracic Surgery

Zhou, Z., Merkus, D., Cheng, C., Duckers, H., Danser, J., & Duncker, D. (2013). Uridine adenosine tetraphosphate is a novel vasodilator in the coronary microcirculation which acts through purinergic P1 but not P2 receptors. Pharmacological Research, 67(1), 10–17. doi:10.1016/j.phrs.2012.09.011