Systemic adenosine given after ischemia protects renal function via A(2a) adenosine receptor activation

Ischemia and reperfusion during renal transplant and aortic surgery result in renal ischemic-reperfusion injury. Previously, we showed that preischemi c adenosine treatment protects renal function via A, adenosine receptor (AR ) activation. In contrast, in the cardiac and pulmonary systems, postischem ic adenosine has potent antiinflammatory attributes and is protective again st reperfusion injury via activation of A(2a) ARs. We questioned whether ad enosine given after an ischemic insult protects renal function in rats, and we sought to determine the AR subtype and intracellular second messengers involved. Rats were randomized to a sham operation, 45 minutes of renal isc hemia and reperfusion and treatments with systemic adenosine or selective A R agonists and antagonists, or treatments of dibutyryl cyclic adenosine mon ophosphate (CAMP) after 45 minutes of renal ischemia but before reperfusion . Forty-five minutes of renal ischemia followed by 24 hours of reperfusion led to severe renal dysfunction as indicated by marked rises in creatinine and histologically evident renal tubular damage. Adenosine treatment after ischemia protected renal function and improved tubular histology. This prot ection was mediated via A(2a) AR activation because the A(2a)-selective AR agonist [4-((N-ethyl-5'-carbamoyadenos-2-yl)-aminoethyl)-phenylpropionic ac id (CGS-21680)] mimics adenosine-induced renal protection, and the A(2a)-se lective AR antagonist [8-(3-chlorostyryl)caffeine (CSC)] blocks adenosine-i nduced renal protection. A(1) or A(3) AR agonists and antagonists did not m imic and block adenosine-induced renal protection. The signaling intermedia tes of A(2a) AR-mediated renal protection appear to include CAMP because di butyryl CAMP mimicked adenosine and CGS-21680 mediated renal protection. Ra t kidneys can be protected against reperfusion injury via postischemic A(2a ) AR activation or CAMP. These data suggest that A(2a) adenosine agonists m ay have clinically beneficial implications when renal ischemia is unavoidab le. (C) 2001 by the National Kidney Foundation, Inc.