Key result
In portal hypertensive and cirrhotic rats, AT1R blockade with losartan attenuated angiotensin II-elicited collateral vasoconstriction, an effect mediated by endothelial NOS.
In portal hypertensive and cirrhotic rats, AT1R mediates collateral vasoconstriction and endothelial NOS participates in the losartan effect, while AT2R influence is negligible.
Should not alter portal hypertension management; hypothesis-generating for AT1R-eNOS collateral control and requires human validation.
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.
No takes yet. Share an insight, caveat, or question.
Huang et al. (2012) studied Portal hypertension and cirrhosis. Angiotensin II receptor blockers (losartan, PD123319) and NOS inhibitors vs. Vehicle was evaluated on Angiotensin II vasoresponsiveness and receptor expression. In portal hypertensive and cirrhotic rats, AT1R blockade with losartan attenuated angiotensin II-elicited collateral vasoconstriction, an effect mediated by endothelial NOS.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: