Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A1 and A3receptors

Renal ischemia and reperfusion during aortic and renal transplant surgery result in ischemic-reperfusion injury. Ischemic preconditioning and adenosine infusion before ischemia protect against ischemic-reperfusion injury in cardiac and skeletal muscle, but these protective phenomena have not been demonstrated in the kidney. Rats were randomized to sham operation, 45-min renal ischemia, ischemic preconditioning with four cycles of 8-min renal ischemia and 5-min reperfusion followed by 45-min renal ischemia, systemic adenosine pretreatment before 45-min renal ischemia, or pretreatments with selective adenosine receptor subtype agonists or antagonists before 45-min renal ischemia. Forty-five minutes of renal ischemia followed by 24 h of reperfusion resulted in marked rises in blood urea nitrogen and creatinine. Ischemic 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 ischemic-reperfusion injury, and A 3 adenosine receptor antagonism protects renal function. We demonstrate for the first time that rat kidneys can be preconditioned 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 adenosine antagonist may have clinically beneficial implications where renal ischemia is unavoidable.