The roles of angiotensin II receptors in the portosystemic collaterals of portal hypertensive and cirrhotic rats

Background/Aims:In liver cirrhosis/portal hypertension, collaterals as varices may bleed and are influenced by vasoresponsiveness. An angiotensin blockade ameliorates portal hypertension but the influence on collaterals is unknown. Methods:Portal hypertension and cirrhosis were induced by portal vein (PVL) and common bile duct ligation (BDL). Hemodynamics, real-time PCR of angiotensin II receptors (AT ₁R, AT ₂R) in the left adrenal vein (LAV, sham) and splenorenal shunt derived from LAV (PVL, BDL) were performed. With an in situcollateral perfusion model, angiotensin II vasoresponsiveness with different preincubations was evaluated: (1) vehicle; (2) AT ₁R blocker losartan; (3) losartan plus nonselective nitric oxide synthase (NOS) inhibitor (N ^ω-nitro-L-arginine); (4) AT ₂R blocker PD123319; (5) PD123319 plus N ^ω-nitro-L- arginine; (6) N ^ω-nitro-L-arginine, and (7) losartan plus inducible NOS inhibitor aminoguanidine. Results: LAV AT ₁R and AT ₂R expression decreased in PVL and BDL rats. Losartan attenuated angiotensin II-elicited vasoconstriction but PD123319 had no effect. N ^ω-nitro-L-arginine but not aminoguanidine reversed the losartan effect. Conclusions:Angiotensin receptors are downregulated in the collateral vessel of portal hypertensive and cirrhotic rats. The AT ₁R blockade attenuates the angiotensin II vasoconstrictive effect, suggesting AT ₁R mediates collateral vasoconstriction and the influence of AT ₂R is negligible. The lack of aminoguanidine influence indicates that endothelial NOS participates in the losartan effect.