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.
Mathie
R T
RT
Department of Surgery, Royal Postgraduate Medical School, London.
Ralevic
V
V
Alexander
B
B
Burnstock
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D000241:Adenosine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester