Control of hepatic carbohydrate metabolism and haemodynamics in perfused rat liver by arterial and portal angiotensin II

Design: Angiotensin II (All; 0.2, 5 and 25 nM) was infused during a single-pass perfusion of a rat liver via both the hepatic artery and the portal vein (portal or arterial All). Infusion occurred both in the absence and in the presence of the AT(1)-receptor-antagonist losartan (1 and 10 mu M). Metabolism: Arterial and portal All increased glucose output and shifted lactate uptake to release. Portal All was 3 (0,2 nM) and 1.5 times (5 and 25 nM) more effective in increasing hepatic glucose release than similar levels of arterial All. However, 0.2, 5 and 25 nM of arterially and portally applied All had a similar level of efficiency in switching lactate uptake to release. The metabolic alterations by arterial and portal All were, however, strongly inhibited by the addition of 1 mu M losartan (an AT(1)-receptor-antagonist) and completely blocked by the presence of 10 mu M losartan. Haemodynamics: Arterial and portal All decreased the flow in the ipsilateral vessels to a similar extent, both demonstrating similar kinetics. Medium and high levels of arterial and portal All caused pronounced flow alterations of the contralateral vessels. The All-dependent reductions of arterial and portal flow were strongly inhibited by the presence of 1 mu M losartan and were stopped by 10 mu M of this blocker. Results: The results demonstrate that arterial and portal All caused alterations in the hepatic metabolism, demonstrating either clear (glucose balance) or no (lactate balance) differences, produced similar reductions of the ipsilateral flow, and pronounced and complex modulations of the contralateral flow.