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Lipopolysaccharide enhanced renal vascular response to endothelin‐1 through ET A overexpression in portal hypertensive rats
Author(s) -
Chuang ChiaoLin,
Huang HuiChun,
Chang ChingChih,
Lee FaYauh,
Wu JawChing,
Lee JingYi,
Hsieh HsianGuey,
Lee ShouDong
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12670
Subject(s) - medicine , endocrinology , kidney , vasoconstriction , endothelin receptor , endothelin 1 , portal hypertension , cirrhosis , receptor
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 ( ET A ) level paralleled with the changes of renal vascular reactivity in LPS ‐treated rats. Compared with SHAM rats, PVL rats showed increased renal ET A and phosphorylated extracellular‐signal‐regulated kinases 1/2 (p‐ ERK 1/2) 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 ET A and subsequent activation of ERK 1/2 signaling.