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

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. 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 μ m ; pA 2 =5.69±0.04). Suramin (100–1000 μ m ) also competitively blocked vasoconstrictor responses to α,β‐methylene ATP, albeit with lower potency (pA 2 =4.79±0.05). In contrast, NF023 (100 μ m ) did not significantly affect contractile responses to noradrenaline or histamine in the saphenous artery. In noradrenaline‐precontracted rabbit isolated thoracic aorta preparations, ATP (3–3000 μ m ) concentration‐dependently induced relaxations via endothelium‐dependent or smooth muscle P2Y‐receptor subtypes. NF023 (30–300 μ m ) failed to block relaxant responses to ATP at endothelium‐dependent P2Y‐receptors, whereas suramin (100–1000 μ m ) did antagonise endothelium‐dependent vasodilator responses to ATP. Neither NF023 (100 μ m ) nor suramin (300 μ m ) influenced vasorelaxant responses to ATP via endothelium‐independent P2Y‐receptors. 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.British Journal of Pharmacology (1997) 120 , 954–960; doi: 10.1038/sj.bjp.0700984