Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.

Abstract

Activated neutrophils have been implicated in the development of ischemia/reperfusion (I/R)-induced renal failure. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a major factor in acute inflammation, is responsible for the activation of neutrophils and for neutrophil chemotaxis to sites of injury. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators. We examined whether the human form of ANP attenuates I/R-induced renal injury by reducing neutrophil activation in a rat model. Male Wistar rats weighing 200-240 g were observed for 24 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP, 0.2 microg/kg/min) beginning immediately after ischemia and continuing for 2 h after reperfusion. CINC-1 and myeloperoxidase (MPO) concentrations were measured to assess activation of the infiltrating neutrophil. Blood urea nitrogen and serum creatinine and urinary N-acetyl beta-d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. alpha-hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. alpha-hANP also reduced I/R-induced increases in the concentrations of blood urea nitrogen and serum creatinine, and improved histopathologic changes, including acute tubular necrosis. These findings indicate that alpha-hANP attenuates I/R-induced acute renal injury, at least in part by reducing neutrophil activation, and may be useful in surgeries, associated with renal ischemia, as well as in renal transplantation.

• Authors: Kousuke Chujo, Masaaki Ueki, Takehiko Asaga, Satoshi Taie
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 215 Issue 3 Pg. 257-66 (Jul 2008) ISSN: 1349-3329 [Electronic] Japan
• PMID: 18648186 (Publication Type: Journal Article)

Chemical References

• Chemokine CXCL1
• Cxcl1 protein, rat
• Atrial Natriuretic Factor
• Creatinine
• Peroxidase
• Hexosaminidases

Topics

• Animals
• Atrial Natriuretic Factor (metabolism)
• Chemokine CXCL1 (metabolism)
• Creatinine (metabolism)
• Hexosaminidases (metabolism)
• Inflammation
• Kidney (injuries, pathology)
• Male
• Models, Biological
• Neutrophil Activation
• Neutrophils (metabolism)
• Peroxidase (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (pathology)