Renal dysfunction secondary to ischemic-reperfusion injury is a serious clinical problem in both aortic and renal transplant anesthesia and surgery. Murry, in 1986, first described the protective effect of """"""""ischemic preconditioning"""""""" in cardiac muscle by showing that multiple brief ischemic periods before prolonged ischemia lessened myocardial dysfunction and infarction size after the reperfusion period. The mechanisms of cardiac ischemic preconditioning are known to involve pre-ischemic A' adenosine receptor activation, protein kinase C (PKC), and pertussis toxin-sensitive G-proteins (G'). We have recently demonstrated that ischemic preconditioning also occurs in the kidney and protects rat renal function against ischemic-reperfusion injury via a signaling pathway involving Gj and PKC. Moreover, adenosine treatment protects against renal ischemicreperfusion injury. Systemic adenosine pretreatment protects rat renal function via a pathway involving A adenosine receptors, Gj and PKC. Pre-ischemic A3 adenosine receptor antagonism and agonism also protect and worsen renal function, respectively. In addition, systemic adenosine given after the ischemic insult also protects renal function against reperfusion injury via A2a adenosine receptor activation. Our major aim is to further elucidate the cellular signal transduction mechanisms of renal protection from the receptor to the transcription factor level with pre- and post-ischemic adenosine treatments employing physiological, cellular and molecular techniques. Based on our in vivo data, we hypothesize that A, adenosine receptor activation and A3 adenosine receptor antagonism lead to protection against the ischemic phase of renal injury, and that A2a adenosine receptor activation attenuates the reperfusion phase of renal ischemic reperfusion injury via distinct cellular signal transduction pathways. Our research will aid in a better understanding of the cellular mechanisms of renal ischemic reperfusion injury. This, in turn, will contribute to improved therapeutic regimens for the protection of renal function in patients.
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