Effects of atrial natriuretic peptide on inter-organ crosstalk among the kidney, lung, and heart in a rat model of renal ischemia-reperfusion injury

Abstract

BackgroundRenal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury and a frequent occurrence in critically ill patients. Renal IRI releases proinflammatory cytokines within the kidney that induce crosstalk between the kidney and other organ systems. Atrial natriuretic peptide (ANP) has anti-inflammatory as well as natriuretic effects and serves important functions as a regulator of blood pressure, fluid homeostasis, and inflammation. The objective of the present study was to elucidate whether ANP post-treatment attenuates kidney-lung-heart crosstalk in a rat model of renal IRI.MethodsIn experiment I, a rat model of unilateral renal IRI with mechanical ventilation was prepared by clamping the left renal pedicle for 30 min. Five minutes after clamping, saline or ANP (0.2 μg/kg/min) was infused. The hemodynamics, arterial blood gases, and plasma concentrations of lactate and potassium were measured at baseline and at 1, 2, and 3 h after declamping. The mRNA expression and localization of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the kidney, lung, and heart were examined. In experiment II, a rat model of bilateral renal IRI without mechanical ventilation was prepared by clamping bilateral renal pedicles for 30 min. Thirty minutes after clamping, lactated Ringer's (LR) solution or ANP (0.2 μg/kg/min) was infused. Plasma concentrations of TNF-α, IL-6, and IL-1β were determined at baseline and at 3 h after declamping.ResultsIn unilateral IRI rats with mechanical ventilation, ANP inhibited the following changes induced by IRI: metabolic acidosis; pulmonary edema; increases in lactate, creatinine, and potassium; and increases in the mRNA expression of TNF-α, IL-1β, and IL-6 in the kidney and lung and IL-1β and IL-6 in the heart. It also attenuated the histological localization of TNF-α, IL-6, and nuclear factor (NF)-κB in the kidney and lung. In bilateral IRI rats without mechanical ventilation, ANP attenuated the IRI-induced increases of the plasma concentrations of potassium, IL-1β, and IL-6.ConclusionsRenal IRI induced injury in remote organs including the lung and the contralateral kidney. ANP post-treatment ameliorated injuries in these organs by direct tissue protective effect and anti-inflammatory effects, which potentially inhibited inter-organ crosstalk.

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review

“…Inotropic agents can be used to improve renal functions in low cardiac output states. Unlike other inotropes, levosimendan is a non-catecholamine calcium sensitizer which has stabilising effect on troponin C to enhance cardiac contractility without increasing myocardial oxygen consumption, leading to haemodynamic stability of myocardium [61] . It has been shown to have beneficial effect in decreasing low cardiac output syndrome and mortality after cardiac surgery [62] .…”

Resveratrol Does Not Protect from Ischemia-Induced Acute Kidney Injury in an in Vivo Rat Model

“…Destabilisation of blood pressure associated with bilateral (and not unilateral) renal ischemia has been described before [21, 22, 36], although to our knowledge studies performing close continuous arterial blood pressure monitoring especially during the clamping period have not been performed by other groups. The mechanisms involved in induction of hypotension during bilateral renal clamping remain unclear, but it is conceivable that this effect is related to interference by the clamping itself with sympathetic nerves surrounding the renal artery as decreasing blood pressure is observed immediately following mechanical manipulation.…”

Atrial natriuretic peptide reduces inflammation and enhances apoptosis in rat acute pancreatitis

“…26 We show here that ANP decreased the nuclear translocation of NF-jB (p65 subunit) and TNF-a intrapancreatic content in AP, consistent with previous studies in immune cells and other cell types. 15,27 The reduction of NF-jB activation induced by ANP in AP was higher in the presence of secretin. Previous studies showed that ANP prevents liver injury induced by ischaemia-reperfusion by reducing NF-jB and TNF-a synthesis and release through NPR-A receptors coupled to guanylyl cyclase activation.…”

“…15 Furthermore, ANP also displays anti-inflammatory effects in the kidney, heart and lung. 27 In the exocrine pancreas, ANP signals preferentially through NRP-C receptors coupled to Gi activation, and regulates intracellular cAMP levels to prevent acinar cell injury. 13,14 Various studies reveal that cAMP is a modulator of NF-jB action, although the positive or negative effect on the transcription factor appears to be highly cell type-and context-dependent, as it is its role in programmed cell death.…”