Activation of sensory neurons reduces ischemia/ reperfusion-induced acute renal injury in rats

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PGI1 produced by endothelial cells improves ischemia/reperfusion-induced acute renal injury by inhibiting leukocyte activation in rat. However, the underlying mechanism of increased PGI2 production is not fully elucidated. Activation of sensory neurons increases endothelial PGI2 production byincreasing calcitonin gene-related peptide (CGRP) in rat hepatic ischemia or reperfusion. We examined here whether activation of sensory neurons increases PGI2 endothelial production, thereby reducing ischemia/reperfusion-induced acute renal injury. Renal tissue level of CGRP and 6-keto-PGF1α a stable metabolite of PGI2, increased after renal ischemia/reperfusion, peaking at 1h after reperfusion. Overexpression of CGRP was also noted at 1 h after reperfusion. Increases in renal tissue levels of 6-keto-PGF1α at 1h after reperfusion were significantly inhibited by pretreatment with capsazepin, CGRP(8-37), indomethacin. Pretreatment with capsazepin, CGRP (8-37), indomethacin, and denervation of primary sensory nerves significantly increased blood urea nitrogen and serum creatinine levels, renal vascular permiabilit6y, renal tissue levels of MPO activity, CINC, and TNF-α, and decreased renal tissue blood flow. However, pretreatment with CGRP significantly improved these changes. Our result suggests activation of sensory neurons in the pathologic process of ischemia/reperfusion-induced acute renal injury. Such activation reduces acute renal injury attenuating inflammatory responses through enhanced endothelial PGEI2 production.