The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo

Abstract

BackgroundThe role of adenosine and ATP in the regulation of hepatic arterial blood flow in the "buffer response" was studied in vitro and in a new in vivo model in the rabbit. The model achieves portal-systemic diversion by insertion of a silicone rubber prosthesis between the portal vein and inferior vena cava and avoids alterations in systemic haemodynamics.ResultsHepatic arterial (HA) blood flow increased in response to reduced portal venous (PV) blood flow, the "buffer response", from 19.4 (3.3) ml min-1 100 g-1 to 25.6 (4.3) ml min-1 100 g-1 (mean (SE), p < 0.05, Student's paired t-test). This represented a buffering capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1 micrograms kg-1-0.5 mg kg-1) elicited immediate increases in HA blood flow to give -log ED50 values of 2.0 and 1.7 mg kg-1 for ATP and adenosine respectively. Injection of ATP and adenosine had no measurable effect on PV flow. In vitro, using an isolated dual-perfused rabbit liver preparation, the addition of 8-phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly inhibited the HA response to intra-arterial adenosine and to mid-range doses of intra-portal or intra-arterial ATP (p < 0.001).ConclusionsIt is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P1-purinoceptors following catabolism of ATP to adenosine.