title: Interference of angiotensin II and enalapril with hepatic blood flow regulation.
abstract: Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 μg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.
authors: Departments of Intensive Care Medicine and.
authors: Adriano J
authors: AJ
authors: Pereira
authors: Departments of Intensive Care Medicine and Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors: Victor
authors: V
authors: Jeger
authors: Visceral Surgery and Medicine, Inselspital/University Hospital, and.
authors: René
authors: R
authors: Fahrner
authors: Departments of Intensive Care Medicine and.
authors: Siamak
authors: S
authors: Djafarzadeh
authors: Departments of Intensive Care Medicine and.
authors: Michael
authors: M
authors: Lensch
authors: Departments of Intensive Care Medicine and.
authors: Jukka
authors: J
authors: Takala
authors: Departments of Intensive Care Medicine and stephan.jakob@insel.ch.
authors: Stephan M
authors: SM
authors: Jakob
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006499:Hepatic Artery / Q000187:drug effects* / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D013552:Swine; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril
keywords: angiotensin II; angiotensin-converting enzyme inhibitor; enalapril; hepatic artery buffer response