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Local and systemic effects of peritoneal lavage with high concentrations of adenosine in rats
E K Jackson1, R S Swamy, W A Herzer
1Center for Clinical Pharmacology, Department of Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. edjt@pitt.edu
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.
Aim:
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.