Lipopolysaccharide enhanced renal vascular response to endothelin-1 through ETA overexpression in portal hypertensive rats.

Journal of gastroenterology and hepatology

PubMedID: 24989426

Chuang CL, Huang HC, Chang CC, Lee FY, Wu JC, Lee JY, Hsieh HG, Lee SD. Lipopolysaccharide enhanced renal vascular response to endothelin-1 through ETA overexpression in portal hypertensive rats. J Gastroenterol Hepatol. 2014;.
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 7th day following surgery. Isolated kidney perfusion was performed at 0.5 hour, or 5 hours 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 hours following endotoxemia. There were extensive up-regulations of inducible nitric oxide synthase in both renal arteries and 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 hour after LPS.

CONCLUSIONS
LPS-induced systemic hypotension induces a paradoxical change of renal vascular response to endothelin-1 between SHAM and PVL rats. LPS-induced renal vascular hyper-reactivity in PVL rats was associated with up-regulation of renal ETA and subsequent activation of ERK1/2 signaling.