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Atrial natriuretic peptide reduces the ischemia/reperfusion-induced renal injury in rats by enhancing sensory neuron activation

Introduction

Although carpertide, a synthetic α-human atrial natriuretic peptide (ANP), reduces ischemia/reperfusion (I/R)-induced tissue injury, the precise therapeutic mechanism(s) remains to be elucidated. Calcitonin gene-related peptide (CGRP) released from sensory neurons reduces I/R-induced liver injury by inhibiting neutrophil activation through an increase in the endothelial production of prostacyclin (PGI2). In the present study, we examined in rats whether ANP reduces I/R-induced renal injury by enhancing sensory neuron activation.

Methods

The right renal vessels were clamped in rats for 45 minutes after left nephrectomy. ANP (0.3 μg/kg/min) was continuously infused from 30 minutes before ischemia to 60 minutes after reperfusion. We attempted to determine whether ANP promotes CGRP release from cultured dorsal root ganglion neurons isolated from adult rats in vitro.

Results

Intravenous infusion of ANP reduced I/R-induced increase in serum levels of blood urea nitrogen and creatinine at 24 hours after reperfusion. ANP inhibited I/R-induced increases in renal tissue levels of TNF and myeloperoxidase at 3 and 6 hours after reperfusion, respectively. ANP significantly enhanced I/R-induced increases in renal tissue levels of CGRP and 6-keto-PGF1α, a stable metabolite of PGI2, at 1 hour after reperfusion. ANP-induced increases in renal tissue levels of CGRP were significantly inhibited by pretreatment with SB366791, a specific vanilloid receptor-1 antagonist. ANP-induced increases in renal tissue levels of 6-keto-PGF1α were significantly inhibited by pretreatment with SB366791, CGRP(8–37), a CGRP receptor antagonist, and indomethacin. Reduction of I/R-induced increases in serum levels of blood urea nitrogen and creatinine and those in renal tissue levels of TNF and myeloperoxidase in rats treated with ANP were completely abrogated by pretreatment with SB366791, CGRP(8–37), and indomethacin. ANP significantly increased CGRP release from dorsal root ganglion neurons in vitro.

Conclusion

These results strongly suggested that ANP might reduce I/R-induced renal injury in rats by inhibiting neutrophil activation through enhancement of sensory neuron activation.

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Harada, N., Okajima, K. & Mizuochi, Y. Atrial natriuretic peptide reduces the ischemia/reperfusion-induced renal injury in rats by enhancing sensory neuron activation. Crit Care 11, P455 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/cc5615

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Keywords

  • Indomethacin
  • Atrial Natriuretic Peptide
  • Dorsal Root Ganglion Neuron
  • Renal Injury
  • SB366791