The transhepatic action of ATP on the hepatic arterial and portal venous vascular beds of the rabbit: the role of nitric oxide.
1. The effect of bolus administration of adenosine 5'-triphosphate (ATP) into the portal vein on hepatic arterial pressure (the transhepatic action of ATP) and portal venous pressure, and the contribution of nitric oxide towards these responses, was studied in the in vitro dual-perfused rabbit liver. 2. At basal tone, hepatic arterial and portal venous vasoconstriction followed ATP injection, while at a tone raised with methoxamine (10(-6)-10(-5) M) ATP caused hepatic arterial vasodilatation, and a phasic vasodilatation followed by vasoconstriction in the portal venous vascular bed. 3. To determine whether the transhepatic arterial dilatation was due to the diffusion of nitric oxide (NO) from the portal venous vasculature, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), an inhibitor of NO synthesis, was infused selectively into the portal vein. L-NAME infusion potentiated portal venous vasoconstriction to ATP (-log M ED50 5.32 +/- 0.31 to 6.51 +/- 0.43, P < 0.05, Student's paired t test) indicating the possible inhibition of a NO-mediated vasodilator component of the portal venous response to ATP. There was, however, no demonstrable difference in the transhepatic arterial vasodilatation induced by ATP during this infusion. 4. Simultaneous perfusion of both the hepatic arterial and portal venous inflows with L-NAME (100 microM) resulted in a significant decrease in the amplitude of hepatic arterial responses to ATP demonstrating that these responses were ultimately mediated by an NO-dependent mechanism. 5. This study has thus demonstrated a vasodilator component of the portal venous response to ATP that is NO-mediated. It also provides evidence that it is not portally-derived NO, but NO released from the hepatic arterial vascular bed, that accounts for the hepatic arterial vasodilatation to intra-portal administration of ATP. This implies that ATP itself, and not a second messenger, diffuses from the portal venous to hepatic arterial vascular bed to elicit the hepatic arterial response.
Browse
D J
DJ
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London.
Mathie
R T
RT
Benjamin
I S
IS
Alexander
B
B
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006499:Hepatic Artery / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester