Adrenomedullin serves a role in the humoral pathway of delayed remote ischemic preconditioning via a hypoxia-inducible factor-1α-associated mechanism

Remote ischemic preconditioning (RIPC) is a minimally invasive method that provides protection by reducing injury to the heart, kidneys, brain and other tissues or organs. RIPC may improve the outcome in patients undergoing surgery. Although the role of RIPC has been studied, the results remain controversial. It is difficult to confirm whether RIPC has a kidney protective effect and the understanding of the preconditioning signal pathway involved remains unclear. In the present study, the effect of RIPC in urology was evaluated. The protection against renal damage was assessed by investigating the potential mediator, hypoxia-inducible factor-1α (HIF-1α), and the functional adrenomedullin (ADM) pathway. Male Sprague-Dawley (SD) rats were used in the present study. The animal model of kidney damage induced by ischemia reperfusion (IR) was used to investigate the protective effect of the acute and delayed phase RIPC. Furthermore, the protective effects of RIPC mediated by a HIF-1α-ADM pathway were assessed. The indexes of renal function and oxidative damage indicators were measured by Cr, BUN, mALB, β2-MG, MPO, MDA and SOD assays, and the expression of HIF-1α and ADM were detected by western blot analysis, immunohistochemistry and ELISA assays. Tubular score, determined using hematoxylin and eosin staining, was used to evaluate renal tissue damage. Applying RIPC prevented IR-induced renal dysfunction and oxidative damage by decreasing Cr, BUN, mALB, β2-MG, MPO, MDA levels and increasing SOD activity. Findings showed that delayed RIPC had an improved effect compared with acute treatment. Delayed RIPC also upregulated the expression of HIF-1α and ADM, indicating that the protective effect of the delayed RIPC may be associated with a HIF-1α-ADM-mediated mechanism. The effect of the delayed RIPC to reduce IR-induced renal damage and increase ADM expression was enhanced by HIF-1α agonists DMOG and BAY 85–3934, whereas the effect was whittled by HIF-1α antagonists YC-1 and 2-MeOE2. Furthermore, receiving ADM also offered protection to the kidney in comparison with the IR+Vehicle group. These findings suggest that RIPC prevents IR-mediated renal damage by HIF-1α via an ADM humoral pathway. In the present study, RIPC provided an effective renal protection. ADM could also offer protection regulated by HIF-1α in renal tissue. However, the mechanism of ADM as a protective factor in RIPC requires further research.