C-type natriuretic peptide prevents kidney injury and attenuates oxidative and inflammatory responses in hemorrhagic shock

Abstract

Oxidative stress induced by hemorrhagic shock (HS) initiates a systemic inflammatory response, which leads to subsequent kidney injury. This study assessed the efficacy of c-type natriuretic peptide (CNP) in attenuating kidney injury in a rat model of hemorrhagic shock and resuscitation (HS/R). Sodium pentobarbital-anesthetized adult male Wistar rats underwent HS induced by the withdrawal of blood to a mean arterial pressure of 30-35 mmHg for 50 min. Then, the animals received CNP (25 μg/kg) or vehicle (saline) intravenously, followed byresuscitation with 1.5 times the shed blood volume in the form of normal saline. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, tissue injury and kidney function were evaluated after resuscitation. CNP infusion reduced the malondialdehyde content, lowered the myeloperoxidase activity and decreased the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the kidney. The histologic injury score and the plasma creatinine concentration were also significantly decreased after CNP treatment compared to the vehicle group. CNP treatment ameliorates oxidative stress, the inflammatory response, and consequently acute kidney injury after HS/R. Thus, CNP may represent a promising strategy to improve resuscitation for the treatment of HS and deserves further investigation.

C-Type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature

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The Role of Natriuretic Peptides in the Regulation of Cardiac Tolerance to Ischemia/Reperfusion and Postinfarction Heart Remodeling

“…It was established that intravenous administration of CNP (25 mg/kg) to rats with hemorrhagic shock prevents an increase in TNF-a, IL-1b and IL-6 content in the kidney. 130 Investigators found that CNP reduces secretion of MCP-1 and plasminogen activator inhibitor-1 (PAI-1) by cardiac fibroblasts. 131 They suggest that a decrease in MCP-1 and PAI-1 secretion is involved in the antifibrotic effect of the peptide.…”

Longitudinal Growth in Rheumatologic Conditions: Current and Emerging Treatments of Growth Delay in Children with Chronic Autoimmune Diseases

“…CNP infusion to this model lowered the myeloperoxidase activity and decreased the expression of TNF-α, IL-6, and IL-1β in the kidneys. CNP treatment suppressed oxidative stress, ameliorated the inflammatory response, and caused acute kidney injury [92]. Investigators suggested that they demonstrated CNP infusion's inhibitory effect on the generation of reactive oxygen species (ROS) and pro-inflammatory cytokines after hemorrhagic shock induction and subsequently suppressed the activation, recruitment, and adherence of neutrophils in the kidney.…”