The action of ATP on the hepatic arterial and portal venous vascular networks of the rabbit liver: the role of adenosine.
ATP is released from blood vessels during periods of hypoxia and may be responsible for hepatic arterial vasodilatation during instances of reduced hepatic portal venous flow. The role of adenosine in ATP-induced vasodilator and vasoconstrictor responses of the hepatic arterial and portal venous vascular networks respectively was studied in the isolated dual-perfused rabbit liver in vitro to ascertain whether ATP could be catabolised to adenosine during transit through the hepatic parenchyma. Intra-arterial and intra-portal injections of ATP (-10 to -4 log mol/100 g liver) resulted in dose-dependent vasodilatation in the hepatic artery and vasoconstriction in the portal vein. Addition of 8-phenyltheophylline (10 microM), a non-selective P1-purinoceptor antagonist, to the hepatic arterial and portal venous perfusate significantly inhibited the hepatic arterial ED50 for responses to intra-arterial injected ATP from -8.70 +/- 0.22 to -7.63 +/- 0.28 log mol/100 g liver (P < 0.001); it also inhibited hepatic arterial responses to, mid-range, portal venous injections of ATP. The data suggest that the hepatic arterial vasodliatation to ATP is partly mediated via catabolism to adenosine and may be an important mechanism during periods of relative hepatic hypoxia associated with portal flow reduction.
Browse
D J
DJ
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Mathie
R T
RT
Benjamin
I S
IS
Alexander
B
B
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006499:Hepatic Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine