The protective role of adenosine in inducing nitric oxide synthesis in rat liver ischemia preconditioning is mediated by activation of adenosine A2 receptors

• Published in: Hepatology (Baltimore, Md.) Vol. 29; no. 1; pp. 126 - 132
• Main Authors: Peralta, Carmen, Hotter, Georgina, Closa, Daniel, Prats, Neus, Xaus, Carme, Gelpí, Emilio, Roselló‐Catafau, Joan
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA W.B. Saunders 01-01-1999; Wiley
• Subjects: Adenosine - pharmacology; Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; Ischemia - metabolism; Ischemia - physiopathology; Ischemic Preconditioning; Liver - blood supply; Liver - enzymology; Liver - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Necrosis; Nitric Oxide - biosynthesis; Other diseases. Semiology; Rats; Rats, Wistar; Receptors, Purinergic P1 - drug effects; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Adenosine; Chemoprophylaxis; Rat; Induction; Liver; Rodentia; Cardiovascular disease; Hepatic disease; Activation; Experimental study; A2 Adenosine receptor; Vascular disease; Vertebrata; Mammalia; Reperfusion; Synthesis; Ischemia; Animal; Nitric oxide; Digestive diseases
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.510290104

This study aims to determine if the protective role of adenosine in liver ischemic preconditioning is mediated by the activation of adenosine receptors and to ascertain which of these receptors is implicated in the process. Administration of adenosine A1
and A2 receptor antagonists to preconditioned animals indicates that hepatic preconditioning is mediated by the activation of adenosine A2 receptors. Propentofylline (an inhibitor of adenosine transport into cells) in the preconditioned group, subjected to previous administration of an adenosine A2 receptor antagonist, prevented the negative effect of the latter on the protection offered by preconditioning. An increase of NO production was detected just immediately after hepatic preconditioning, and the administration of an adenosine A2 receptor antagonist to the preconditioning group prevented this increase, thus abolishing the protective effect of preconditioning. However, the administration of a NO donor to the preconditioned group subjected to previous administration of the adenosine A2 receptor antagonist was able to maintain the preconditioning effects. In conclusion, these results indicate that, in preconditioning, the protective effect of adenosine could be a result of an increase in extracellular adenosine. This in turn would induce the activation of adenosine A2
receptors, which, by eliciting an increase in NO generation, would protect against the injury associated with hepatic ischemia‐reperfusion.