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Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. In decompensated cirrhosis, presence of ascites is associated with reduced renal perfusion. Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFR\u03b2) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFR\u03b2-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. <jats:italic>In vitro<\/jats:italic> collagen contraction assays tested biological activity on LX2 cells. Hemodynamics were analyzed in BDL and CCl<jats:sub>4<\/jats:sub> cirrhotic rats 3\u2009h, 6\u2009h and 24\u2009h after i.v. administration of Y27pPBHSA (0.5\/1\u2009mg\/kg b.w). Phosphorylation of moesin and myosin light chain (MLC) assessed ROCK activity in liver, femoral muscle, mesenteric artery, kidney and heart. Three Y27 molecules were coupled to pPBHSA as confirmed by HPLC\/MS, which was sufficient to relax LX2 cells. <jats:italic>In vivo<\/jats:italic>, Y27pPBHSA-treated rats exhibited lower portal pressure, hepatic vascular resistance without effect on systemic vascular resistance, but a tendency towards lower cardiac output compared to non-treated cirrhotic rats. Y27pPBHSA reduced intrahepatic resistance by reduction of phosphorylation of moesin and MLC in Y27pPBHSA-treated cirrhotic rats. Y27pPBHSA was found in the liver of rats up to 6\u2009hours after its injection, in the HSC demonstrated by double-immunostainings. Interestingly, Y27pPBHSA increased renal arterial flow over time combined with an antifibrotic effect as shown by decreased renal <jats:italic>acta2<\/jats:italic> and c<jats:italic>ol1a1<\/jats:italic> mRNA expression. Therefore, targeting the ROCK inhibitor Y27 to PDGFR\u03b2 decreases portal pressure with potential beneficial effects in the kidney. 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