Research

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

Dominic J Browse¹ , Robert T Mathie² , Irving S Benjamin¹ and Barry Alexander¹

¹  Liver Sciences Unit, Academic Department of Surgery, GKT School of Medicine and Dentistry, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK

²  Division of Surgery, Imperial College School of Medicine, Hammersmith Hospital, 150 Du Cane Road, London W12 ONN, UK

author email corresponding author email

Comparative Hepatology 2003, 2:9doi:10.1186/1476-5926-2-9

Published:	26 November 2003

Abstract

Background

The 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.

Results

Hepatic 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).

Conclusions

It is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P₁-purinoceptors following catabolism of ATP to adenosine.