Control of hepatic carbohydrate metabolism and haemodynamics in perfused rat liver by arterial and portal angiotensin II.
METHODS
Angiotensin II (AII; 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 AII). Infusion occurred both in the absence and in the presence of the AT1-receptor-antagonist losartan (1 and 10 microM).
Arterial and portal AII increased glucose output and shifted lactate uptake to release. Portal AII 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 AII. However, 0.2, 5 and 25 nM of arterially and portally applied AII had a similar level of efficiency in switching lactate uptake to release. The metabolic alterations by arterial and portal AII were, however, strongly inhibited by the addition of 1 microM losartan (an AT1-receptor-antagonist) and completely blocked by the presence of 10 microM losartan.
Arterial and portal AII decreased the flow in the ipsilateral vessels to a similar extent, both demonstrating similar kinetics. Medium and high levels of arterial and portal AII caused pronounced flow alterations of the contralateral vessels. The AII-dependent reductions of arterial and portal flow were strongly inhibited by the presence of 1 microM losartan and were stopped by 10 microM of this blocker.


RESULTS
The results demonstrate that arterial and portal AII 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.
Reisenleiter
F
F
Institut für Klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, Germany.
Katz
N
N
Gardemann
A
A
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006499:Hepatic Artery / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007773:Lactates / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects*; D019808:Losartan; D008297:Male; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007773:Lactates; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005947:Glucose; D019808:Losartan