Hepatic conversion of angiotensin I and the portal hypertensive response to angiotensin II in normal and regenerating liver.

BACKGROUND AND AIM: Angiotensin I (AI) and angiotensin II (AII) induce a portal hypertensive response (PHR) and the liver is able to convert AI into AII to trough the action of the angiotensin-converting enzyme (ACE). Our purpose was to characterize angiotensin I liver conversion. METHODS: AI, AII or angiotensin (1-7) were used in monovascular or bivascular perfusions. RESULTS: The maximum gain in portal pressure induced by AII took place significantly earlier (P = 0.031) than that occurring after an equimolar AI infusion. The AI-induced PHR was abolished both by captopril or losartan, whereas the AII-induced PHR was not affected by captopril, but was abolished by losartan. Angiotensin (1-7) has no hemodynamic effect in the perfused liver. After partial hepatectomy, the AII-PHR pattern changes from a rapid return to baseline values to a pattern where there was no return to baseline values (3-7 days ex-surgery). In the bivascular perfusion system when AII was infused in the arterial branch in the retrograde mode of perfusion (peptide available only to the periportal zone), the PHR was at least 50% of that obtained when the prograde mode was used (peptide available to the periportal and perivenous zones). CONCLUSION: AI does not induce PHR; this effect is a result of its mandatory conversion into AII by the ACE and the sequential action of AII on the AII receptor type 1 located in the hepatic periportal zone. AII induced PHR pattern changes during liver regeneration.

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.