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Contribution of hepatic adenosine A 1 receptors to renal dysfunction associated with acute liver injury in rats
Author(s) -
Ming Zhi,
Fan YiJun,
Yang Xi,
Lautt W. Wayne
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21336
Subject(s) - hepatorenal syndrome , medicine , endocrinology , adenosine , renal blood flow , adenosine a1 receptor , kidney , renal function , adenosine receptor , acute kidney injury , cirrhosis , receptor , agonist
Abstract Acute liver injury is associated with renal insufficiency, whose mechanism may be related to activation of the hepatorenal reflex. We previously showed that intrahepatic adenosine is involved in activation of the hepatorenal reflex to restrict urine production in both healthy rats and in rats with cirrhosis. The aim of the present study was to test the hypothesis that activation of intrahepatic adenosine receptors is involved in the pathogenesis of the renal insufficiency seen in acute liver injury. Acute liver injury was induced by intraperitoneal injection of thioacetamide (TAA, 500 mg/kg) in rats. The animals were instrumented 24 hours later to monitor systemic, hepatic, and renal circulation and urine production. Severe liver injury developed following TAA insult, which was associated with renal insufficiency, as demonstrated by decreased (∼25%) renal arterial blood flow, a lower (∼30%) glomerular filtration rate, and decreased urine production. Further, the increase in urine production following volume expansion challenge was inhibited. Intraportal, but not intravenous, administration of a nonselective adenosine receptor antagonist, 8‐phenyltheophylline, improved urine production. To specify receptor subtype, the effects of 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, an adenosine A 1 receptor antagonist) and 3,7‐dimethyl‐1‐propargylxanthine (DMPX, an adenosine A 2 receptor antagonist) were compared. Intraportal but not intravenous administration of DPCPX greatly improved impaired renal function induced by acute liver injury, and this beneficial effect was blunted in rats with liver denervation. In contrast, neither intraportal nor intravenous administration of DMPX showed significant improvement in renal function. In conclusion , an activated hepatorenal reflex, triggered by intrahepatic adenosine A 1 receptors, contributed to the pathogenesis of the water and sodium retention associated with acute liver injury. (H EPATOLOGY 2006;44:813–822.)