Adenosine receptor blockade reduces splanchnic hyperemia in cirrhotic rats.
To explore a possible role for adenosine in the pathogenesis of the splanchnic hyperemia of cirrhosis, we administered 8-phenyltheophylline, a specific adenosine receptor antagonist, to rats with biliary cirrhosis caused by bile duct ligation and to control sham-operated rats. Micro-Doppler flow studies showed that a 10-mumol/kg dose of 8-phenyltheophylline completely abolished the superior mesenteric hyperemic response to infusions of exogenous adenosine in both cirrhotic and control rats. Analysis of regional blood flows by radioactive microspheres demonstrated that this dose of 8-phenyltheophylline in cirrhotic rats significantly increased portal tributary vascular resistance by 60% and decreased portal tributary blood flow by 26%. This decrease was entirely the result of a 42% reduction in the intestinal blood flow. 8-phenyltheophylline did not affect cardiac output, arterial pressure or any other extrasplanchnic hemodynamic variables in cirrhotic rats. No detectable effect of 8-phenyltheophylline was seen in sham-operated rats. These results suggest that adenosine may be involved in the genesis of splanchnic hyperemia in cirrhotic rats.
Lee
S S
SS
Gastroenterology Research Group, University of Calgary, Alberta, Canada.
Chilton
E L
EL
Pak
J M
JM
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000503:physiopathology; D008297:Male; D058914:Purinergic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D058914:Purinergic Antagonists; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine