Experimental Study Of Losartan In Portal Hypertensive Gastropathy Rats

Objective: To determine the expression and immunolocalization ofangiotensinⅡreceptor 1 in the stomach wall of portal hypertensivegastropathy(PHG) rats, and investigate the effects after angiotensinⅡreceptor 1 antagonist losartan treatment and the underlying mechanism.Methods: Sprague-Dawley rats underwent partial portal vein ligationand deligating left suprarenal vein to develop PHG, sham operation to becontrol. Losartan was applied by stomach irritation with 100mg/Kg×dafter operation or model finished 6 weeks or 4 weeks respectively tomake treatment group and prevention group. Portal vein pressure (PVP),the level of angiotensinⅡin blood, gastric injury index(GI), pathologicaldiagnosis integral(PI) were measured. In situ hybridization was used todetermine the expression and immunolocalization of angiotensinⅡreceptor 1 in rat stomach wall. Detect VEGF and CD34 in rat stomachwall by immunohistochemistry and calculate the microvessel density.Identify the expression of MMP-2 and TIMP-2 mRNA by RT-PCR.Results: 1. This mothod of developing PHG is operative, achieve-ment ratio is 100%, with portal vein pressure elevation; 2. The data ofexperimental groups is higher than control group ,and that of treatmentgroup and prevention group is no significant difference; 3. PVP, GI andPI of treatment group and prevention group are evidently reduced (P＜0.01), the level of angiotensinⅡin blood increases markedly(P＜0.01);4. The expression of VEGF and MMP-2 mRNA and MVD are reducednotablely while TIMP-2 is up (P＜0.01). CD34 expression was foundmainly on new capillary blood vessels of gastric mucosa and submucouslayer, and that is weak on gastric muscular wall; 5. The expression ofangiotensinⅡreceptor 1 are negative in control group, rise up signifi-cantly in model group, and decrease remarkably in treatment group andprevention group.Conclusion: 1. This mothod of developing PHG is easy, simple, andeffective. 2. The expression of angiotensinⅡreceptor 1 rise up in portalhypertensive gastropathy, and capillary blood vessels of gastric submu-cous layer ascend. 3. Losartan can reduce PVP, inhibits activation ofangiotensinⅡreceptor 1 and angiogenesis in gastric submucous layer bydeceasing the expression of MMP-2 mRNA and VEGF by increasingexpression of TIMP-2mRNA. Losartan has therapeutic effect on PHG.