Local and systemic effects of peritoneal lavage with high concentrations of adenosine in rats.
BACKGROUND
Adenosine exerts actions which may be beneficial in treating diseases of the gastrointestinal tract. However, administered systemically, adenosine causes a 'stress reaction' and may adversely affect blood pressure and cardiac and renal function.


OBJECTIVE
To determine whether peritoneal lavage with adenosine provides pharmacological levels of adenosine in the intestines without elevating adenosine levels in the systemic circulation.


METHODS
Rats received an intramesenteric artery infusion of angiotensin II (30 ng/min) plus methoxamine (3 microg/min) to reduce mesenteric blood flow by approximately 60%, and adenosine solutions were instilled into the abdominal cavity. In a second study, microdialysis probes were placed in the mesenteric vein and aortic arch of rats, and the peritoneal cavity was continuously lavaged with adenosine solutions.


RESULTS
High concentrations (10(-3)M) of adenosine normalized the mesenteric blood flow without affecting blood pressure or heart rate. High concentrations of adenosine (10(-3)M) induced micromolar levels of adenosine and inosine in the mesenteric vein, without affecting adenosine or inosine levels in the aorta.


CONCLUSIONS
Peritoneal lavage with high concentrations of adenosine provides pharmacological levels of adenosine in the gastrointestinal tract without systemic side-effects. Peritoneal lavage with high concentrations of adenosine may be useful for the treatment of a number of diseases of the gastrointestinal tract.
Jackson
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EK
Center for Clinical Pharmacology, Department of Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. edjt@pitt.edu
Swamy
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Herzer
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D000241:Adenosine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010533:Peritoneal Lavage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014970:Xanthines / Q000378:metabolism
D002317:Cardiovascular Agents; D014662:Vasoconstrictor Agents; D014970:Xanthines; D000804:Angiotensin II; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D007288:Inosine; D000241:Adenosine