Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

Figures

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  Figure 1. Biochemical data of partial portal vein ligation (PVL) rats treated by vehicle (control), valsartan, or LCZ696 (sacubitril/valsartan). Valsartan and LCZ696 significantly decreased the plasma levels of alanine aminotransferase (ALT) (both P < 0.05). In addition, valsartan decreased the plasma level of aspartate aminotransferase (AST) (P < 0.05). The total bilirubin and creatinine levels were not significantly affected by valsartan and LCZ696.

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  Figure 2. Liver histology and immunochemical staining of PVL rats treated by vehicle (control), valsartan, or LCZ696. The representative hematoxylin and eosin staining images show similar architecture of liver tissue among these 3 groups (magnification 200×, upper panel). Many Cluster of Differentiation 68 (CD68)-positive staining cells (the representative brown cell with irregular shape as indicated by green arrow) were noted in the control group. In contrast, they were nearly absent in those treated by valsartan and LCZ696 (magnification 200×, lower panel).

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  Figure 3. Portal-systemic shunting degree of PVL rats treated with vehicle, valsartan, or LCZ696. Valsartan and LCZ696 did not significantly affect the shunting degree (P > 0.05).

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  Figure 4. Hepatic protein expressions of control, valsartan-, LCZ696-treated PVL rats. The densitometric quantification and representative Western blot images are shown. The upper panel reveals that the endothelial-1 (ET-1) protein expression was significantly downregulated by LCZ696 compared to the control group. The vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-1, and COX-2 protein expressions were not significantly different among control, valsartan-, and LCZ696-treated PVL rats. The lower panel indicates that the phosphorylated-endothelial nitric oxide synthase (eNOS) protein expressions were downregulated by valsartan and LCZ696 treatments. The phosphorylated-nuclear factor kappa B (NFκB) p65, phosphorylated-antinuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and phosphorylated-inducible nitric oxide synthase (iNOS) protein expressions were not affected by valsartan and LCZ696.