PMID- 24989426 OWN - NLM STAT- MEDLINE DCOM- 20150910 LR - 20141224 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 30 IP - 1 DP - 2015 Jan TI - Lipopolysaccharide enhanced renal vascular response to endothelin-1 through ETA overexpression in portal hypertensive rats. PG - 199-207 LID - 10.1111/jgh.12670 [doi] AB - BACKGROUND AND AIM: Hypo-perfusion resulting from intense renal vasoconstriction is traditionally contributed to renal dysfunction in advanced liver disease, although cumulative studies demonstrated renal vasodilatation with impaired vascular contractility to endogenous vasoconstrictors in portal hypertension and compensated liver cirrhosis. The pathophysiology of altered renal hemodynamics remains unclear. This study, using a rat model of portal hypertension with superimposed endotoxemia, was designed to delineate the evolution of renal vascular reactivity and vaso-regulatory gene expression during liver disease progression. METHODS: Rats were randomized into sham surgery (SHAM) or partial portal vein ligation (PVL). Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS) on the seventh day following surgery. Isolated kidney perfusion was performed at 0.5 h or 5 h after LPS to evaluate renal vascular response to endothelin-1. RESULTS: In contrast to impaired vascular contractility of SHAM rats, PVL rats displayed enhanced renal vascular reactivity to endothelin-1 at 5 h following endotoxemia. There were extensive upregulations of inducible nitric oxide synthase in kidney tissues of endotoxemic rats. The changes of renal endothelin receptor type A (ETA ) level paralleled with the changes of renal vascular reactivity in LPS-treated rats. Compared with SHAM rats, PVL rats showed increased renal ETA and phosphorylated extracellular-signal-regulated kinases 1/2 (p-ERK1/2) at 5 h after LPS. CONCLUSION: LPS-induced systemic hypotension induces a paradoxical change of renal vascular response to endothelin-1 between SHAM and PVL rats. LPS-induced renal vascular hyperreactivity in PVL rats was associated with upregulation of renal ETA and subsequent activation of ERK1/2 signaling. CI - (c) 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd. FAU - Chuang, Chiao-Lin AU - Chuang CL AD - Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. FAU - Huang, Hui-Chun AU - Huang HC FAU - Chang, Ching-Chih AU - Chang CC FAU - Lee, Fa-Yauh AU - Lee FY FAU - Wu, Jaw-Ching AU - Wu JC FAU - Lee, Jing-Yi AU - Lee JY FAU - Hsieh, Hsian-Guey AU - Hsieh HG FAU - Lee, Shou-Dong AU - Lee SD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Endothelin-1) RN - 0 (Lipopolysaccharides) RN - 0 (Receptor, Endothelin A) SB - IM MH - Animals MH - Disease Models, Animal MH - Endothelin-1/*physiology MH - Gene Expression Regulation MH - Hypertension, Portal/*genetics/*physiopathology MH - Kidney/*blood supply MH - Lipopolysaccharides/*pharmacology MH - MAP Kinase Signaling System/genetics/physiology MH - Male MH - Rats, Sprague-Dawley MH - Receptor, Endothelin A/*genetics/*physiology MH - Up-Regulation MH - Vasoconstriction/drug effects/*genetics/*physiology OTO - NOTNLM OT - endothelin receptor type A OT - lipopolysaccharide OT - partial portal vein ligation OT - portal hypertension OT - renal vascular reactivity EDAT- 2014/07/06 06:00 MHDA- 2015/09/12 06:00 CRDT- 2014/07/04 06:00 PHST- 2014/05/26 00:00 [accepted] PHST- 2014/07/04 06:00 [entrez] PHST- 2014/07/06 06:00 [pubmed] PHST- 2015/09/12 06:00 [medline] AID - 10.1111/jgh.12670 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2015 Jan;30(1):199-207. doi: 10.1111/jgh.12670.