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 (approximately 25%) renal arterial blood flow, a lower (approximately 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.