CONTROL OF HEPATIC CARBOHYDRATE-METABOLISM AND HEMODYNAMICS IN PERFUSED-RAT-LIVER BY ARTERIAL AND PORTAL ANGIOTENSIN-II

Design: Angiotensin II (All; 0.2, 5 and 25 nM) was infused during a si ngle-pass perfusion of a rat liver via both the hepatic artery and the portal vein (portal or arterial All). Infusion occurred both in the a bsence 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 glu cose 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 ef ficiency in switching lactate uptake to release. The metabolic alterat ions by arterial and portal All were, however, strongly inhibited by t he addition of 1 mu M losartan (an AT(1)-receptor-antagonist) and comp letely blocked by the presence of 10 mu M losartan. Haemodynamics: Art erial 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 los artan and were stopped by 10 mu M of this blocker. Results: The result s demonstrate that arterial and portal All caused alterations in the h epatic metabolism, demonstrating either clear (glucose balance) or no (lactate balance) differences, produced similar reductions of the ipsi lateral flow, and pronounced and complex modulations of the contralate ral flow.