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 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.
Lee
H T
HT
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. tl128@columbia.edu
Emala
C W
CW
D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology; D019194:Ischemic Preconditioning; D007668:Kidney / Q000473:pathology; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000517:prevention & control; D013997:Time Factors
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D000241:Adenosine