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.
|頁（從 - 到）||160-168|
|期刊||Journal of Vascular Research|
|出版狀態||Published - 4月 2012|