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)naphth alene-1,3,5-trisulphonic acid), and its parent compound suramin were i nvestigated on vasoconstrictor responses to alpha,beta-methylene ATP i n rabbit isolated saphenous artery and vasodilator responses to ATP in noradrenaline-precontracted rabbit isolated thoracic aorta. 2 In rabb it isolated saphenous artery, alpha,beta-methylene ATP-induced vasocon strictor responses via P2X-receptors were concentration-dependently an d competitively antagonised by NF023 (30-300 mu M; pA(2) = 5.69+/-0.04 ). Suramin (100-1000 mu M) also competitively blocked vasoconstrictor responses to alpha,beta-methylene ATP, albeit with lower potency (pA(2 ) = 4.79+/-0.05). In contrast, NF023 (100 mu M) did not significantly affect contractile responses to noradrenaline or histamine in the saph enous artery. 3 In noradrenaline-precontracted rabbit isolated thoraci c aorta preparations, ATP (3-3000 mu M) concentration-dependently indu ced relaxations via endothelium-dependent or smooth muscle P2Y-recepto r subtypes. NF023 (30-300 mu M) failed to block relaxant responses to ATP at endothelium-dependent P2Y-receptors, whereas suramin (100-1000 mu M) did antagonise endothelium-dependent vasodilator responses to AT P. Neither NF023 (100 mu M) nor suramin (300 mu M) influenced vasorela xant responses to ATP via endothelium-independent P2Y-receptors. 4 In conclusion, this study outlines the selectivity of NF023 as an effecti ve P2X-receptor antagonist in rabbit isolated blood vessels without af fecting endothelium-dependent or endothelium-independent P2Y-receptor subtypes, adrenoceptors or histamine receptors.