title: 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.affiliation: Department of Anesthesiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Chujo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Asaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Taie
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D006596:Hexosaminidases / Q000378:metabolism; D007249:Inflammation; D007668:Kidney / Q000293:injuries* / Q000473:pathology*; D008297:Male; D008954:Models, Biological; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D009195:Peroxidase; D006596:Hexosaminidases