Nitric oxide is the mediator of ATP-induced dilatation of the rabbit hepatic arterial vascular bed.

1. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery (HA) and portal vein (PV) at constant flows of 23 +/- 1 and 77 +/- 1 ml min-1 100 g-1 respectively. The tone of the preparation was raised with noradrenaline (concentration: 10 microM). 2. Dose-response curves for the vasodilatation produced by adenosine 5'-triphosphate (ATP), acetylcholine (ACh), adenosine, and sodium nitroprusside (SNP) were obtained following injection into the HA supply. Injections were then repeated in the presence of the L-arginine to nitric oxide pathway inhibitors N-monomethyl-L-arginine (L-NMMA, n = 6) and N-nitro-L-arginine methyl ester (L-NAME, n = 4) at concentrations of 30 microM and 100 microM for each inhibitor. 3. Both L-NMMA and L-NAME antagonized the responses to ATP and ACh; L-NAME was 2-3 times more potent than L-NMMA as an inhibitor of these endothelium-dependent vasodilatations. Neither L-NMMA nor L-NAME attenuated responses of the endothelium-independent vasodilators, adenosine and SNP. 4. These results indicate that nitric oxide is the mediator of ATP-induced vasodilatation in the HA vascular bed of the rabbit and that the receptor responsible for the release of nitric oxide, the P2y-purinoceptor, is located predominantly on the endothelium.