Blockade of intrahepatic adenosine receptors improves urine excretion in cirrhotic rats induced by thioacetamide.
OBJECTIVE
In healthy rats, we recently showed that reduced intrahepatic portal blood flow leads to activation of hepatic adenosine receptors and a nerve-induced decrease in urine production. We hypothesize that the impaired urine excretion in liver cirrhosis is related to an increase in intrahepatic adenosine.


METHODS
Anesthetized normal and thioacetamide-induced cirrhotic rats were instrumented for the measurement of urine flow, hepatic portal venous blood flow, and renal arterial blood flow. 8-Phenyltheophylline was used to block adenosine receptors.


RESULTS
Compared to normal rats, cirrhotic rats had a lower baseline urine flow (P<0.05). In both normal and cirrhotic rats, intraportal but not intravenous administration of 8-phenyltheophylline increased urine flow. Saline overload in normal rats increased urine flow (from 6.8+/-0.6 to 42.2+/-4.6 microlmin(-1)) and this ability was impaired in cirrhotic rats (from 3.9+/-0.4 to 6.2+/-0.9 microlmin(-1)). Intraportal, but not intravenous, administration of 8-phenyltheophylline partially restored the renal ability to excrete the saline load.


CONCLUSIONS
Impaired renal ability to excrete urine in liver cirrhosis is related to the activation of intrahepatic adenosine receptors, and this is consistent with our previous data showing renal regulation through a hepatorenal neural mechanism activated by intrahepatic adenosine.
Ming
Zhi
Z
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A210-753 McDermot Avenue, Winnipeg, Man., Canada.
Fan
Yi-Jun
YJ
Yang
Xi
X
Lautt
W Wayne
WW
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000652:urine*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013853:Thioacetamide; D014556:Urine
D058915:Purinergic P1 Receptor Antagonists; D013853:Thioacetamide; D012964:Sodium; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine