Atrial Natriuretic Peptide Group Research Articles

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis

BackgroundAtrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics.Methods and resultsThe study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II.ConclusionsThe study demonstrates ANP’s potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP’s effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.

The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity.

ResumoFundamento A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas.Objetivo Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade.Métodos 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19).Resultados Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento.Conclusão Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

Atrial Natriuretic Peptide in the Prevention of Postoperative Acute Renal Dysfunction in Patients Undergoing Heart Transplantation - An Investigator-Driven, Single-Center, Blinded, Randomized and Placebo-Controlled Trial

Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complication after heart transplantation (HTx) that is associated with increased morbidity and mortality. When used for treatment of AKI, infusion of atrial natriuretic peptide (ANP) has been shown to increase renal blood flow and glomerular filtration rate (GFR) after complicated cardiac surgery and in cyclosporine-induced AKI after HTx. Furthermore, it was shown that ANP reduced the probability of dialysis in cardiac surgery-associated AKI. The aim of this investigation was to evaluate whether ANP infusion could prevent or mitigate acute renal dysfunction after HTx. Methods After approval of Ethical Review Board and the Swedish Medical Products Agency, 72 adult patients undergoing HTx were included after informed consent. The patients were randomized to receive either ANP or placebo (saline) by a web-based computerized random-number generator. The anesthesia/intensive staff and physicians were blinded to the allocated treatment throughout the entire study. After induction of anesthesia, a continuous intravenous infusion of either ANP (HANP1000®, Daichii Sankyo Propharma, Japan) at a dose of 50 ng/kg/min or the equivalent volume of placebo (saline) was started. The administration of the study drugs continued for five postop days, or until the patient died or treatment with dialysis was started. Inclusion has been completed. Endpoints The primary end-point was measured mGFR at day five. mGFR was assessed by the infusion clearance of 52Cr-EDTA. The difference in mGFR between groups was estimated using intention-to-treat and per-protocol analyses. To detect a 30% higher mGFR in the ANP group, 31 patients per group would be required, assuming a 80% power and a two-sided error of 0.05. To compensate for drop-outs and for the use of nonparametric tests, we included 35 randomised patients per group. Secondary end-points were: the incidence of postoperative AKI (KDIGO criteria), daily postoperative serum creatinine, need for dialysis, intra- and postoperative diuresis, the use of diuretics, length of ICU and hospital stay, ICU mortality and 30-days mortality, length of mechanical ventilation, incidence of hypotension and arrhythmias and inotropic score.

Therapeutic role of atrial natriuretic peptide in early treatment of traumatic hemorrhagic shock

The biological effect of atrial natriuretic peptide (ANP) in traumatic hemorrhagic shock (THS) is unknown. This study was to evaluate whether ANP therapy can show organ protection in THS. Thirty male Sprague-Dawley rats were divided into three groups: ANP group, sham group, and control group. Pressure-controlled THS was induced in rats in ANP group and control group. ANP at a rate of 0.025 μg/kg/min was infused in ANP group during near-80 min of shock. After that, animals were resuscitated for 60 min and observed until 24 h. Hemodynamic parameters during shock and resuscitation were measured. Serum levels of ANP and lactate dehydrogenase, tissue oxidative stress and inflammatory factors, as well as liver and kidney function were determined. Tissue apoptosis was also assessed. There was no statistically significant difference between ANP group and control group in arterial pressure throughout the 150 min monitoring period. Blood urea nitrogen at 90 min and 24 h in ANP group was significantly lower than control group. Alanine transaminase and aspartate aminotransferase activity at 90 min in control group were significantly higher than that in sham group. However, hepatic enzyme activity at 90 min in ANP group was not significantly different compared with sham or control group. After 24 h, myocardial expression of caspase 3 protein in ANP group was significantly reduced compared with control group. Jejunal and hepatic Malondialdehyde was increased following ANP treatment. ANP therapy during early THS has no significant adverse effect on hemodynamics but can exert oxidative stress and certain protective effect on multiple organs. Our study may shed light on the novel therapy of THS with regard to organ protection. The mechanisms underlying the organ protection require further study.

Effects of atrial natriuretic peptide on renal function during cardiopulmonary bypass: a randomized pig model.

Acute kidney injury is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In this experimental animal study, we evaluated the effects of atrial natriuretic peptide (ANP) on renal function, perfusion, oxygenation and tubular injury during CPB. Twenty pigs were blindly randomized to continuous infusion of either ANP (50 ng/kg/min) or placebo before, during and after CPB. Renal blood flow as well as cortical and medullary perfusion was measured. Blood was repeatedly sampled from the renal vein. Glomerular filtration rate was measured by infusion clearance of 51Cr-EDTA. Glomerular filtration rate was higher (P < 0.001), whereas renal blood flow or renal oxygen delivery was not affected by ANP during CPB. Renal oxygen consumption did not differ between groups during CPB, whereas renal oxygen extraction was higher in the ANP group (P = 0.03). Urine flow and sodium excretion were higher in the ANP group during CPB. Blood flow in the renal medulla, but not in the cortex, dropped during CPB, an effect that was not seen in the animals that received ANP. ANP improved renal function during CPB. Despite impaired renal oxygenation, ANP did not cause tubular injury, suggesting a renoprotective effect of ANP during CPB. Also, CPB induced a selectively reduced blood flow in the renal medulla, an effect that was counteracted by ANP.

Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and\xa0meta-analysis

BackgroundTheoretically, atrial natriuretic peptide (ANP), especially low-dose ANP, is beneficial in acute kidney injury (AKI). In this study, we examined whether low-dose ANP is effective in preventing or treating AKI by conducting an updated systematic review for randomized controlled trials (RCTs).MethodWe searched the Excerpta Medica database (EMBASE), PubMed, and Cochrane CENTRAL databases for RCTs that compare the effects of low-dose ANP (≤ 50 ng/kg/min) with a placebo or conventional therapy in at-risk patients or patients with AKI. The primary outcome was the incidence of new AKI (in prevention RCTs), while the secondary outcomes were in-hospital mortality rate, renal replacement therapy (RRT) requirement, length of hospital and intensive care unit (ICU) stay, incidence of hypotension, and peak serum creatinine levels. The risk-of-bias was evaluated using the Cochrane Collaboration risk-of-bias tool. Trial sequential analysis (TSA) was used for each outcome of interest.ResultsA total of 18 RCTs (16 prevention and two treatment trials) fulfilled our inclusion criteria. In prevention RCTs, the incidence of new AKI was significantly low in the low-dose ANP group (relative risk [RR] = 0.51; 95% confidence interval [CI] = 0.36–0.72; P = 0.0001) compared to the control group. In addition, the low-dose ANP group showed a significantly reduced RRT requirement in both prevention (RR = 0.17; 95% CI = 0.04–0.64; P = 0.009) and treatment (RR = 0.43; 95% CI = 0.20–0.93; P = 0.03) RCTs. Among secondary outcomes, in some cases, low-dose ANP was associated with a reduction in ICU and in-hospital stay. The risk-of-bias assessment and TSA results indicated that the sample sizes and qualities of the RCTs were insufficient to conclude the efficacy of low-dose ANP.ConclusionLow-dose ANP might be effective in preventing or treating AKI. However, the evidence accumulated so far is not strong enough to demonstrate ANP’s beneficial effects. The next step is to elucidate the effects of low-dose ANP by conducting multicenter, high-quality, large-sample RCTs.Trial registrationPROSPERO registry CRD42017068568. Registered 20 June 2017.

Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke.

Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after tMCAO. Apoptotic cell death and expression of natriuretic peptide receptors (NPR-A and NPR-C), K+ channels (KATP, KV and BKCa), and PI3K/Akt and MAPK/ERK1/2 signaling pathways were analyzed. Significant improvement in neurofunctional status, associated to reduction in infarct and edema volumes, was shown in the high-dose ANP group. As to the molecular mechanisms analyzed, high-dose ANP: 1) reduced caspase-3-mediated apoptosis; 2) did not modify the expression of NPR-A and NPR-C, which had been downregulated by the ischemic insult; 3) induced a significant reversion of ischemia-downregulated KATP channel expression; and 4) induced a significant reversion of ischemia-upregulated pERK2/ERK2 expression ratio. In conclusion, ANP exerts a significant protective role in terms of both improvement of neurofunctional status and reduction in infarct volume. Modulation of ANP on some molecular mechanisms involved in ischemia-induced apoptotic cell death (KATP channels and MAPK/ERK1/2 signaling pathway) could account, at least in part, for its beneficial effect. Therefore, ANP should be considered as a potential adjunctive neuroprotective agent improving stroke outcome after successful reperfusion interventions.

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery–associated acute kidney injury: A multicenter randomized controlled trial

PurposeTo evaluate the effects of atrial natriuretic peptide (ANP) on renal function and medical costs in patients with acute kidney injury (AKI) associated with cardiac surgery. Materials and methodsThe Japanese trial for AKI in Post-cardiovascular surgery patients by ANP (JAPAN) was a prospective, multicenter, randomized, double-blind, placebo-controlled study conducted in 11 hospitals in Japan. Acute kidney injury was defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. The patients were randomly assigned to receive ANP (0.02 μg kg−1 min−1) or placebo. The primary end point was a change in renal function. The secondary end points were a need for renal replacement therapy, the lengths of intensive care unit and hospital stays, and medical costs incurred over the 90-day follow-up. ResultsOf the 77 randomized patients, 37 were in the ANP group and 40 were in the placebo group. Although ANP significantly (P = .018) increased urine output, it did not significantly improve renal function compared with placebo. There were no significant differences between the groups in the renal replacement therapy rate, the lengths of the intensive care unit and hospital stays, or medical costs. ConclusionAtrial natriuretic peptide infusion did not show a renoprotective effect or cost-saving effect in the treatment of cardiac surgery–associated AKI.

The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock.

Background and Aims:The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock.Material and Methods:A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP.Results:In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L.Conclusion:In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect.

Exhaustive atrial natriuretic peptide on mouse heart antioxidant and secretion mechanism

Objective To investigate plasma atrial natriuretic peptide (ANP) secretion in mice exhaustive swimming and antioxidant mechanisms.Methods The experimental mice were grouped,let loaded swimming,and after exhaustive tests in mice plasma ANP,malondialdehyde (MDA),lactic acid (LD) and lactate dehydrogenase (LDH) levels.Results The levels of LD (1.69 ± 0.29) mmol/g prot,LDH (23.69 ±5.28) U/mg prot,ANP (13.65 ± 1.69) mg/L of exhausted group mouse heart were significantly higher,the difference was statistically significant (P ＜ 0.05).ANP on hydrogen peroxide (H2O2)-induced cardiac tissue injury has a protective effect,while LY83583 blockers disrupt the kind of protection,resulting in mice LD,LDH and MDA levels increased,compared with the ANP group,the difference was statistically significant (P ＜ 0.05).Conclusion ANP on the heart has some antioxidant effects,to a certain extent,protect the heart from damage,the release pathway mainly through cyclic guanosine monophosphate (cGMP)-protein kinase C (PKC) signaling pathway implementation. Key words: Atrial natriuretic peptide ; Exhaustive mice ; Cardiac antioxidant; Secretion mechanism

GW24-e1783 The experimental study of protective effects of Atrial Natriuretic Peptide (ANP) Injection on the cultured human umbilial vein endothelial cells injured by hypoxia-reoxygenation

ObjectivesTo study the protective effects of Atrial Natriuretic Peptide (ANP) Injection on the cultured human umbilial vein endothelial cells injured by hypoxia-reoxygenationMethodshypoxia-reoxygenation group (n = 6): cells were cultured in...

Atrial natriuretic peptide modulates the proliferation of human gastric cancer cells via KCNQ1 expression

Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that regulates mammalian blood volume and blood pressure. ANP signaling through NP receptor A (NPR-A)/cyclic guanosine 3′5′-monophosphate (cGMP)/ cGMP-dependent protein kinase (PKG) activates various downstream effectors involved in cell growth, apoptosis, proliferation and inflammation. Evidence has shown the critical role of plasma K+ channels in the regulation of tumor cell proliferation. However, the role of ANP in the proliferation of gastric cancer cells is not clear. In the present study, the expression of NPR-A in the human gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS cells were investigated using western blotting, immunofluorescence, qPCR and patch clamp assays. The K+ current was also analyzed in the effect of ANP on the proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS cell line. Lower concentrations of ANP promoted the proliferation of the AGS cells, although higher concentrations decreased their proliferation. Significant increases in the levels of cGMP activity were observed in the AGS cells treated with 10−10, 10−9 and 10−8 M ANP compared with the controls, but no significant differences were observed in the 10−7 and 10−6 M ANP groups. The patch clamp results showed that 10−9 M ANP significantly increased the tetraethylammonium (TEA)- and 293B-sensitive K+ current, while 10−6 M ANP significantly decreased the TEA- and 293B-sensitive K+ current. The results showed that 10−10 and 10−9 M ANP significantly upregulated the expression of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10−7 and 10−6 M ANP significantly downregulated the expression of KCNQ1. The data indicated that lower and higher concentrations of ANP have opposite effects on the proliferation of AGS cells through cGMP-dependent or -independent pathways. KCNQ1 upregulation and downregulation by lower and higher concentrations of ANP, respectively, have separate effects on the promotion and inhibition of proliferation.

Atrial natriuretic peptide reduces hepatic ischemia–reperfusion injury in rabbits

Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 μg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

Effect of low-dose human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer: A double-blind, placebo-controlled study

We previously reported that patients with preoperative B-type natriuretic peptide levels of 30 pg/mL or more have increased risk of postoperative atrial fibrillation after pulmonary resection. This study evaluated the effects of human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. A prospective, randomized study was conducted with 40 patients who had preoperative elevated B-type natriuretic peptide (≥ 30 pg/mL) and underwent a scheduled pulmonary resection for lung cancer. Results were compared between patients who received low-dose human atrial natriuretic peptide and those who received a placebo. The primary end point was the incidence of postoperative atrial fibrillation during the first 4 days after surgery. The incidence of postoperative atrial fibrillation was significantly lower in the human atrial natriuretic peptide group than in the placebo group (10% vs 60%; P < .001). Patients in the human atrial natriuretic peptide group also showed significantly lower white blood cell counts and C-reactive protein levels after surgery. Continuous infusion of low-dose human atrial natriuretic peptide during lung cancer surgery had a prophylactic effect against postoperative atrial fibrillation after pulmonary resection in patients with preoperative elevation of B-type natriuretic peptide levels. A larger sample size is needed to establish the safety and efficacy of this intervention.

The experimental study of protective effects of atrial natriuretic peptide (ANP) injection on the cultured human umbilical vein endothelial cells injured by hypoxia-reoxygenation

ObjectiveTo study the protective effects of Atrial Natriuretic Peptide (ANP) Injection on the cultured human umbilical vein endothelial cells injured by hypoxia-reoxygenation.MethodsHypoxia-reoxygenation group (n=6): cells were cultured in the hypoxia...

Atrial natriuretic peptide for preventing and treating acute kidney injury

Acute kidney injury (AKI) is common in hospitalised patients and is associated with significant morbidity and mortality. Despite recent advances, outcomes have not substantially changed in the last four decades. Atrial natriuretic peptide (ANP) has shown promise in animal studies, however randomised controlled trials (RCTs) have shown inconsistent clinical benefits. To assess the benefits and harms of ANP for preventing and treating AKI. We searched CENTRAL, MEDLINE and EMBASE and reference lists of retrieved articles. RCTs that investigated all forms of ANP versus any other treatment in adult hospitalised patients with or "at risk" of AKI. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). Outcomes were analysed separately for low and high dose ANP for preventing or treating AKI. Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. Low (but not high) dose ANP was associated with a reduced need for RRT in the prevention studies (RR 0.32, 95% CI 0.14 to 0.71). Length of hospital and ICU stay were significantly shorter in the low dose ANP group. For established AKI, there was no difference in mortality with either low or high dose ANP. Low (but not high) dose ANP was associated with a reduction in the need for RRT (RR 0.54, 95% CI 0.30 to 0.98). High dose ANP was associated with more adverse events (hypotension, arrhythmias). After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies (RR 0.56, 95% CI 0.32 to 0.99), but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery (RR 0.35, 95% CI 0.18 to 0.70). ANP was not associated with outcome improvement in either radiocontrast nephropathy or oliguric AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI and should be further explored in these two settings. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.

Post-ischemic Infusion of Atrial Natriuretic Peptide Attenuates Warm Ischemia–Reperfusion Injury in Rat Lung

The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung during ischemia. In this study we investigated the effect on lung ischemia-reperfusion injury of administering synthetic ANP (carperitide) at the onset of reperfusion after warm ischemia. An isolated rat lung perfusion model was used. The rats were allocated into three groups: the control group; the ANP group; and the sham group. In the control and ANP groups, the heart-lung block was exposed to 60 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. At the onset of reperfusion, either saline or ANP was added to the perfusate. In the sham group, lungs were continuously perfused without ischemia and only saline was added to the perfusate. ANP significantly reduced pulmonary vascular resistance and pulmonary edema, and improved oxygenation. It also significantly increased cGMP levels in reperfused lungs. Histologically, lungs in the ANP group showed significantly fewer signs of injury and fewer cells demonstrated apoptotic changes or single-stranded DNA than lungs in the control group. Our results indicate that ANP administered at the onset of reperfusion increases cGMP in lung tissue and attenuates warm ischemia-reperfusion injury in isolated perfused rat lung.

Renal Protective Effects and the Prevention of Contrast-Induced Nephropathy by Atrial Natriuretic Peptide

This study was designed to examine the protective effects of atrial natriuretic peptide (ANP) on contrast-induced nephropathy (CIN) after coronary angiography. Contrast-induced nephropathy is a common complication after angiography. Some studies have shown that ANP has renal protective effects, but the beneficial effects for CIN prevention remain to be clearly shown. In a prospective, controlled, randomized trial in 254 consecutive patients with serum creatinine concentrations of > or =1.3 mg/dl, patients received either ANP (0.042 microg/kg/min; ANP group, n = 126) or Ringer solution alone (control group, n = 128). Treatment of either type was initiated 4 to 6 h before angiography and continued for 48 h. There were no significant differences in age, sex, diabetes mellitus, or baseline serum creatinine level between the 2 groups. The prevalence of CIN, defined as a 25% increase in creatinine or an increase in creatinine of > or =0.5 mg/dl from baseline within 48 h, was significantly lower in the ANP group than in the control group (3.2% vs. 11.7%, respectively; p = 0.015). Multivariate analysis revealed that the use of >155 ml of contrast medium (odds ratio: 6.89; p < 0.001) and ANP treatment (odds ratio: 0.24; p = 0.016) were significant predictors of developing CIN. The incidence of an increase in creatinine of > or =25% or of > or =0.5 mg/dl from baseline at 1 month was also significantly lower in the ANP group than in the control group (p = 0.006). In addition to hydration, ANP administration is effective in the prevention of CIN in patients with chronic renal failure, and the effect was maintained for 1 month.

Atrial Natriuretic Peptide for Management of Acute Kidney Injury

Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI). The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI. Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies. There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.