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- Title
The Roles of Angiotensin II Receptors in the Portosystemic Collaterals of Portal Hypertensive and Cirrhotic Rats.
- Authors
Huang, Hui-Chun; Chang, Ching-Chih; Wang, Sun-Sang; Lee, Fa-Yauh; Teng, Tzu-Hua; Lee, Jing-Yi; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong
- Abstract
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 (AT1R, AT2R) 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) AT1R blocker losartan; (3) losartan plus nonselective nitric oxide synthase (NOS) inhibitor (Nω-nitro-L-arginine); (4) AT2R blocker PD123319; (5) PD123319 plus Nω-nitro-L-arginine; (6) Nω-nitro-L-arginine, and (7) losartan plus inducible NOS inhibitor aminoguanidine. Results: LAV AT1R and AT2R expression decreased in PVL and BDL rats. Losartan attenuated angiotensin II-elicited vasoconstriction but PD123319 had no effect. Nω-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 AT1R blockade attenuates the angiotensin II vasoconstrictive effect, suggesting AT1R mediates collateral vasoconstriction and the influence of AT2R is negligible. The lack of aminoguanidine influence indicates that endothelial NOS participates in the losartan effect. Copyright © 2012 S. Karger AG, Basel
- Subjects
ANGIOTENSIN II; ANGIOTENSIN receptors; PORTAL hypertension; CIRRHOSIS of the liver; HEMODYNAMICS; LABORATORY rats
- Publication
Journal of Vascular Research, 2012, Vol 49, Issue 2, p160
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000332347