Vasoconstrictor responses via P2X-receptors are selectively antagonized by NF023 in rabbit isolated aorta and saphenous artery

1. The effects of NF023, the symmetrical 3′-urea of 8-(benzamido)naphthalene-1,3,5-trisulphonic acid), and its parent compound suramin were investigated on vasoconstrictor responses to α,β-methylene ATP in rabbit isolated saphenous artery and vasodilator responses to ATP in noradrenaline-precontracted rabbit isolated thoracic aorta.
2. In rabbit isolated saphenous artery, α,β-methylene ATP-induced vasoconstrictor responses via P2X-receptors were concentration-dependently and competitively antagonised by NF023 (30–300 μM; pA₂=5.69±0.04). Suramin (100–1000 μM) also competitively blocked vasoconstrictor responses to α,β-methylene ATP, albeit with lower potency (pA₂=4.79±0.05). In contrast, NF023 (100 μM) did not significantly affect contractile responses to noradrenaline or histamine in the saphenous artery.
3. In noradrenaline-precontracted rabbit isolated thoracic aorta preparations, ATP (3–3000 μM) concentration-dependently induced relaxations via endothelium-dependent or smooth muscle P2Y-receptor subtypes. NF023 (30–300 μM) failed to block relaxant responses to ATP at endothelium-dependent P2Y-receptors, whereas suramin (100–1000 μM) did antagonise endothelium-dependent vasodilator responses to ATP. Neither NF023 (100 μM) nor suramin (300 μM) influenced vasorelaxant responses to ATP via endothelium-independent P2Y-receptors.
4. In conclusion, this study outlines the selectivity of NF023 as an effective P2X-receptor antagonist in rabbit isolated blood vessels without affecting endothelium-dependent or endothelium-independent P2Y-receptor subtypes, adrenoceptors or histamine receptors.