Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors

Renal ischemia and reperfusion during aortic and renal transplant surgery r esult in ischemic-reperfusion injury. Ischemic preconditioning and adenosin e infusion before ischemia protect against ischemic-reperfusion injury in c ardiac and skeletal muscle, but these protective phenomena have not been de monstrated in the kidney. Rats were randomized to sham operation, 45-min re nal ischemia, ischemic preconditioning with four cycles of 8-min renal isch emia and 5-min reperfusion followed by 45-min renal ischemia, systemic aden osine pretreatment before 45-min renal ischemia, or pretreatments with sele ctive adenosine receptor subtype agonists or antagonists before 45-min rena l ischemia. Forty-five minutes of renal ischemia followed by 24 h of reperf usion resulted in marked rises in blood urea nitrogen and creatinine. Ische mic preconditioning and adenosine pretreatment protected renal function and improved renal morphology. A(1) adenosine receptor activation mimics and A (1) adenosine antagonism blocks adenosine-induced protection. In addition, A(3) adenosine receptor activation before renal ischemia worsens renal isch emic-reperfusion injury, and A(3) adenosine receptor antagonism protects re nal function. We demonstrate for the first time that rat kidneys can be pre conditioned to attenuate ischemic-reperfusion injury and adenosine infusion before ischemic insult protects renal function via A(1) adenosine receptor activation. Our data suggest that an A(1) adenosine agonist and A(3) adeno sine antagonist may have clinically beneficial implications where renal isc hemia is unavoidable.