Hemodynamic and metabolic effects of angiotensin II on the liver.
To ascertain the mechanism of interaction between angiotensins (AI and AII) and the liver, an angiotensin-converting enzyme inhibitor (captopril) and a receptor antagonist (losartan) were used. Monovascular or bivascular liver perfusion was used to assess both hemodynamic (portal and arterial hypertensive responses) and metabolic (glucose production and oxygen consumption) effects. Microphysiometry was used for isolated liver cell assays to assess AII or losartan membrane receptor-mediated interaction. Captopril abolishes portal hypertensive response (PHR) to AI but not the AII effect. AII infused via the portal pathway promotes calcium-dependent PHR but not a hypertensive response in the arterial pathway (AHR); when infused into the arterial pathway AII promotes calcium-dependent PHR and AHR. Losartan infused into the portal vein abolishes PHR to AII but not the metabolic response; when infused via both pathways it abolishes the hypertensive responses and inhibits the metabolic effects. Isolated liver cells specifically respond to AII. Sinusoidal cells, but not hepatocytes, respond to 10 nM losartan. We conclude that AI has to be converted to AII to produce PHR. Quiescent stellate cells interacts in vitro with AII and losartan. Hemodynamic responses to AII are losartan-dependent but metabolic responses are partially losartan-independent. AII hemodynamic actions are mainly presinusoidal.
Nascimento
Ecio Alves
EA
Department of Biochemistry, Universidade Estadual de Maringá, Paraná, Brazil.
Gioli-Pereira
Luciana
L
Carvalho
Leda Teixeira
LT
Santos
Edson Lucas
EL
Pesquero
João Bosco
JB
Kouyoumdjian
Maria
M
Borges
Durval Rosa
DR
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan