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 alphahuman ANP (α -hANP, 0.2 μ g/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 β -d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. α -hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. α -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 α -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.human atrial natriuretic peptide; neutrophils; kidney; ischemia/reperfusion; cytokine-induced neutrophil chemoattractant-1. Tohoku

Brain Natriuretic Peptide is Not Reno-Protective during Renal Ischemia-Reperfusion Injury in the Rat

“…Natriuretic peptides also increase glomerular filtration rate (GFR) by selectively dilating renal afferent arterioles and constricting renal efferent arterioles [2]. In a rodent model of renal I/R injury, animals treated with natriuretic peptide exhibited less renal injury due to decreased activation and infiltration of neutrophils [3].…”

D-Ribose Attenuates Ischemia/Reperfusion-Induced Renal Injury by Reducing Neutrophil Activation in Rats

“…In our previous study, renal I/R injury in the control group resulted in a marked increase in the CINC-1 concentrations at 2 h after reperfusion, and then gradually decreased to pre-injury concentrations (Ueki et al 2007;Chujo et al 2008). As shown in Fig.…”

“…Furthermore, MPO concentrations in the control group increased from the pre-injury concentrations at 6 h after reperfusion, and then gradually decreased to the pre-injury concentrations in the control group (Ueki et al 2007;Chujo et al 2008). When D-ribose was administered at a dose of 400 mg/kg, MPO concentrations decreased significantly as compared with the control group at 6 h after reperfusion ( p = 0.0008, Fig.…”

Urinary Fructose-1,6-Bisphosphatase (FBP-1,6) and N-Acetyl-β-Hexosaminidase (HEX) in Monitoring Kidney Transplantation - Literature Review

“…A 4-fold (significantly) higher level of HEX excretion in the recipients compared with the donors, falling to 2-fold (significantly) higher level after 6 hours, and only tendening to increase after 24 h after transplantation, was observed (Bugge et al, 1999). HEX is a specific indicator of ischemia/reperfusion injury of proximal tubules and attenuation of this injury by atrial natriuretic peptide (Chujo et al, 2008). During rejection in 92% of renal allografts, a significant increase in total HEX activity, and decrease in urinary activity of HEX A, with simultaneous increase in activity of HEX B, and intermediary forms of HEX, was observed (Whiting et al, 1983).…”

“…Urinary HEX activity increases from several to dozens of times after damage to the epithelium of proximal convoluted tubules cells (Rustom et al, 1998). As cells of renal proximal convoluted tubules are very sensitive to hypoxia, all pathological states occurring with hypoxia, lead to dysfunction of the epithelium of renal proximal convoluted tubules, and leakage of HEX into urine (Chujo et al, 2008). The kidneys are critical targets for toxicity induced by heavy metals e.g.…”