Serum Atrial Natriuretic Peptide Research Articles

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Correlation of Atrial Natriuretic peptide (ANP) coding gene (NPPA) and Human Hypertension

Atrial natriuretic peptide (ANP) is a polypeptide hormone secreted by atrial muscle cells that has an endogenous antagonistic effect on the renin-angiotensin-aldosterone system (RAAS). It is believed to regulate salt and fluid balance and blood pressure. Blood samples (150) from males aged less than 20 to 55 years were collected from Al-Salam and Ibn-Sena Teaching Hospital in Mosul from 1/2/2022 to 1/9/2022. These samples, 5ml that include healthy and previously blood hypertension-diagnosed patients, were put into two tubes for hormonal and molecular study and divided into three classes: Control, which includes 50 samples from healthy individuals; hypertension without treatment patients 40 individuals and patients with treatment 60 individuals. Each class was divided into five groups according to their age. group (1) less than 20, group (2) 20-29, group (3) 30-39, group (4) 40-49 and group (5) 50-59 years. Serum ANP hormone concentration was measured, and the results revealed significant differences at between patients and healthy control groups. Hormone concentration had decreased in the 1,2 group while increased in groups 3,4,5 of treated and untreated patients compared with control groups with different group concentrations ranging from 28.86-23.16 pg/ml, indicating the effect of aging on hormone concentration. Also, the results revealed a different hormone concentration in untreated patient's groups that ranged between 12.97-28 pg./ml while the concentration of treated patient's groups ranged between 12.97-33.36 pg/ml, these differences in hormone concentration in all groups revealed the effect interference of aging and treatments that had a direct effect on the hormone concentration. Besides, the Amplicon copy numbers of the ANP coding gene (Nppa gene), considered an essential indicator of gene activities utilizing the real-time technique, showed a significant increase in patient groups, especially group (5) of both treated and untreated, compared with control. These results concluded that this hormone had an essential correlation with hypertension.

Comparative observation of changes in natriuretic peptides before and after interventional therapy for congenital heart disease

OBJECTIVE: To explore changes in the plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with left-to-right shunt congenital heart disease (CHD) before and in the early stage after interventional occlusion and to evaluate the clinical significance. METHODS: Among 97 patients with left-to-right shunt CHD undergoing interventional occlusion, 34 cases had a VSD (ventricular septal defect), 35 cases had an ASD (atrial septal defect), and 28 cases had PDA (patent ductus arteriosus). Another 20 normal adults formed the control group. An ELISA was used to determine the plasma ANP and BNP levels before and on the third day after the operation to evaluate their correlations with cardiac functions and the defect size. RESULTS: The plasma ANP and BNP levels of patients with left-to-right shunt CHD were increased compared with those of the normal control group (P< 0.01), and the plasma ANP and BNP levels were decreased on the third day after interventional occlusion compared with the preoperative levels (P< 0.05). The plasma ANP and BNP levels were correlated with the New York Heart Association (NYHA) grade, left ventricular ejection fraction and defect diameter (P< 0.05). CONCLUSION: Patients with left-to-right congenital heart disease exhibit activation of ANP and BNP, which can be alleviated in the early stage after intervention occlusion. Left-to-right shunt congenital heart disease is given priority over atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Early traditional methods included repair or correction by open heart surgery under extracorporeal circulation (also known as cardiopulmonary bypass, CPB). However, interventional therapy has become a developing trend for the treatment of congenital heart disease since 1967, when Porstmann et al. [1]. reported the transcatheter closure of ASD for the first time. The application of the AMPLATZER occluder, which is a simple and feasible method, has improved the safety of the treatment and enabled the therapeutic effect to reach ideal levels. The natriuretic peptide (NP) family consists of the atrial natriuretic polypeptide (ANP), the brain natriuretic peptide, which is also known as the B type natriuretic peptide (BNP), the C type natriuretic peptide (CNP), the renal natriuretic peptide (RNP) and the D type natriuretic peptide (DNP). These family members are similar in structure, have strong natriuretic, diuretic and vasodilative effects and antagonize the activity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nerve. Together, the natriuretic peptides sensitively and specifically reflect the ventricular function state. Although all types of congenital heart disease differ in anatomical structure, they all contain the common features of heart failure. This study detected changes in the serum ANP and BNP levels in patients with left-to-right shunt congenital heart disease before and on the third day after interventional occlusion to evaluate the early changes in left-to-right shunt congenital heart disease after interventional occlusion through neuroendocrine.

Safety and feasibility of left atrial appendage inversion in swine: A proof-of-concept study for potential therapy to prevent embolic stroke.

Objective: Left atrial appendage (LAA) occlusion or exclusion has been used in patients with atrial fibrillation to prevent stroke, but the techniques and devices have shortcomings. This study aims to validate the safety and feasibility of a novel LAA inversion procedure. Methods: LAA inversion procedures were done in six pigs. Before the procedure and at 8 weeks postoperatively, heart rate, blood pressure, and electrocardiogram (ECG) were recorded. The serum concentration of atrial natriuretic peptide (ANP) was measured. The LAA was observed and measured by transesophageal echocardiogram (TEE) and intracardiac echocardiogram (ICE). At 8 weeks after LAA inversion, the animal was euthanized. The heart was collected for morphology and histology, including hematoxylin-eosin, Masson trichrome, and immunofluorescence staining. Results: TEE and ICE showed that LAA was inverted, and the inversion was maintained during the 8-week study duration. Food intake, body weight gain, heart rate, blood pressure, ECG, and serum ANP level were comparable before and after the procedure. Morphology and histological staining showed that there was no obvious inflammation or thrombus. Tissue remodeling and fibrosis were observed at the LAA inverted site. Conclusion: The inversion of LAA effectively eliminates the dead space of LAA and thus may reduce the risk of embolic stroke. The novel procedure is safe and feasible, but the efficacy in reducing embolization remains to be demonstrated in future studies.

Regulation of atrial natriuretic peptide secretion in cardiomyocytes by Rab3a and zDHHC9-mediated palmitoylation of Rab3gap1.

Natriuretic peptides are secreted by the heart in response to cardiovascular stress to reduce blood pressure and volume and thus there is interest in bolstering natriuretic peptide levels to improve outcomes in heart failure. We uncovered novel functions for the Golgi S-acyltransferase, zDHHC9, in regulating atrial natriuretic peptide (ANP) secretion in cardiomyocytes. zDHHC9 palmitoylates Rab3 GTPase activating protein 1 (Rab3gap1) in cardiomyocytes both in vitro and in vivo, resulting in enhanced Rab3gap1 retention at the Golgi, elevation of Rab3a-GTP levels, and a profound expansion of Rab3a-positive vesicles at the cardiomyocyte periphery in contrast to predominant Golgi localization in control cardiomyocytes. However, these zDHHC9-induced effects were associated with impairment of ANP release, suggesting zDHHC9-mediated disruption of Rab3a nucleotide cycling interferes with exocytosis of ANP. Consistent with this, overexpression of wildtype Rab3gap1 that promotes Rab3a GTP:GDP turnover greatly accelerated ANP secretion whereas overexpression of a Rab3gap1 GAP-defective mutant lacked this effect. Phenylephrine (PE) treatment induced Rab3gap1 palmitoylation, Rab3a-GTP levels, and Rab3a-containing post-Golgi vesicles, but this was associated with a substantial and well-established increase in ANP biosynthesis and secretion. Knockdown of zDHHC9 blunted PE-induced Rab3a GTP-loading and expansion of Rab3a-associated vesicles but evoked even greater PE-stimulated ANP release, suggesting Rab3gap1 palmitoylation provides an intrinsic regulatory mechanism to modulate cardiomyocyte exocytosis and ANP secretion. Importantly, Rab3a localized to atrial granules in vivo and transgenic mice with cardiomyocyte-specific overexpression of zDHHC9 exhibited dysregulated atrial granule morphology, accumulation of ANP in atrial cardiomyocytes, and reduced serum ANP levels, suggesting a defect in ANP release in zDHHC9-overexpressing hearts. Collectively, these data implicate zDHHC9-mediated palmitoylation of Rab3gap1 in disruption of Rab3a GTP:GDP cycling in cardiomyocytes required for proper ANP release, thereby highlighting novel roles for zDHHC9, Rab3gap1, and Rab3a in modulating ANP secretion.

Diagnostic value of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their correlation with lipoproteins in dogs with myxomatous mitral valve disease

BackgroundMyxomatous mitral valve disease (MMVD) is the most common diagnosed cardiovascular disease in dogs. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) tests are used to diagnose congestive heart failure, but there are conflicting reports about their value in diagnosing the subclinical stages of MMVD in dogs. Moreover, the diagnostic value of blood lipoproteins in dogs with MMVD is still unclear. The purpose of this study was to assess the serum concentrations of ANP, BNP and lipoproteins of dogs with MMVD and to evaluate the correlation of the levels of ANP and BNP with lipoproteins.ResultsThis study was performed on 24 dogs with MMVD and 10 healthy dogs. Dogs with MMVD were classified in to stages B1 (n = 11), B2 (n = 6), C (n = 4) and D (n = 3) groups according to the classification suggested by American College of Veterinary Internal Medicine guidelines. Our results showed that the mean serum BNP levels were significantly increased for all MMVD groups compared to control dogs. The mean serum ANP levels for the stage B2, C and D groups were significantly higher than the control group, while the mean serum ANP concentrations did not differ significantly between the stage B1 and control groups. An increase in BNP level was observed in 87.5% of patients. Although BNP concentrations were elevated in 100% of dogs with stages C, D and B2, high BNP was observed in 72.72% of dogs with stage B1. Regarding ANP, 58.33% of patients had an increase in ANP. However, elevated ANP levels were found in only 27.27% of patients in stage B1, while increased ANP levels were observed in 66.66 and 100% of patients in stage B2 and C/D groups respectively. Also, in all patients with MMVD, the mean serum concentrations of high-density lipoprotein cholesterol (HDL-C) were approximately 1.7 to 2 times significantly lower than the control group. Additionally, the mean serum low-density lipoprotein cholesterol (LDL-C) increased significantly (1.9-2.7 times) compared to the control group.There was a significant inverse correlation between HDL-C and BNP, and HDL-C and ANP. LDL-C showed a significant positive correlation with BNP, and ANP. Also, LDL-C, but not HDL-C, had a significant positive correlation with LA/AO ratio, LVIDd, LVIDdN and VHS. BNP and ANP showed a significant positive correlation with LA/AO, LVIDd, LVIDdN and VHS.ConclusionsSerum BNP has a greater diagnostic value than serum ANP in dogs with MMVD. In addition, serum BNP can be used to determine the subclinical stages of B1 and B2 MMVD. This study also suggests that dogs with subclinical MMVD, showed an increase in BNP along with a decrease in HDL-C and an increase in LDL-C, which are known to be risk factors for cardiovascular diseases in human. However, it seems that high LDL-C is more involved in the pathogenesis of MMVD than low HDL-C. Therefore, periodic testing of serum lipoproteins is recommended in high-risk patients, even if total cholesterol levels are normal.

Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation

Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey, Polygala tenuifolia, Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear. This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism. PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice. KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues. KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed ferroptosis in hippocampal neurons and myocardiocytes.

Different Protein Sources Enhance 18FDG-PET/MR Uptake of Brown Adipocytes in Male Subjects.

Background: The unique ability of brown adipocytes to increase metabolic rate suggests that they could be targeted as an obesity treatment. Objective: The objective of the study was to search for new dietary factors that may enhance brown adipose tissue (BAT) activity. Methods: The study group comprised 28 healthy non-smoking males, aged 21–42 years old. All volunteers underwent a physical examination and a 75 g oral glucose tolerance test (75g-OGTT). Serum atrial and brain natriuretic peptide (ANP, BNP), PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16) and eukaryotic translation initiation factor 4E (eIF4E) measurements were taken, and 3-day food intake diaries were completed. Body composition measurements were assessed using dual-energy X-ray absorptiometry (DXA) scanning and bioimpedance methods. An fluorodeoxyglucose-18 (FDG-18) uptake in BAT was assessed by positron emission tomography/magnetic resonance (PET/MR) in all participants after 2 h cold exposure. The results were adjusted for age, daily energy intake, and DXA lean mass. Results: Subjects with detectable BAT (BAT(+)) were characterized by a higher percentage of energy obtained from dietary protein and fat and higher muscle mass (p = 0.01, p = 0.02 and p = 0.04, respectively). In the BAT(+) group, animal protein intake was positively associated (p= 0.04), whereas the plant protein intake negatively correlated with BAT activity (p = 0.03). Additionally, the presence of BAT was inversely associated with BNP concentration in the 2 h of cold exposure (p = 0.002). Conclusion: The outcomes of our study suggest that different macronutrient consumption may be a new way to modulate BAT activity leading to weight reduction.

Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones located in atria granules. Both peptides respond to cardiac pressure and volume dynamics and accordingly serve as translation biomarkers for the clinical treatment of heart failure. Serum ANP and BNP play central secretary roles in blood pressure and cardiac output regulation and have proven utility as differential biomarkers of cardiovascular proficiency and drug-induced maladaptation, yet both peptides are impervious to exercise-induced hypertrophy. We employed immunoelectron microscopy to examine the effects of 28 days of chronic swim exercise or administration of a PPARγ agonist on atrial granules and their stored natriuretic peptides in Sprague Dawley rats. Chronic swimming and drug treatment both resulted in a 15% increase in heart weight compared with controls, with no treatment effects on perinuclear granule area in the left atria (LAs). Drug treatment resulted in larger size granules with greater BNP density in the right atria. Comparing swimming and PPARγ agonist treatment effects on ANP:BNP granule density ratios between atrial chambers revealed a shift toward a greater proportion of ANP than BNP in LAs of swim-trained rats. These data suggest a distinction in the population of ANP and BNP after chronic swim or PPARγ that makes it a novel metric for the differentiation of pathological and physiological hypertrophy.

Serum Atrial Natriuretic Peptide, NPPA Promoter Methylation, and Cardiovascular Disease: A 10-year Follow-Up Study in Chinese Adults.

Background:Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population.Methods:Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene (NPPA) promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and NPPA promoter methylation with incident CVD.Results:During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03–1.44, P = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30–0.82, P = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at NPPA promoter as a whole was significantly associated with incident CVD (P < 0.05).Conclusions:Increased proANP and hypomethylation at NPPA promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of CVD.

Resuscitation of hemorrhagic shock using normal saline does not damage the glycocalyx in the immediate resuscitation phase.

OBJECTIVES:The objectives were to study the effect of aggressive resuscitation using normal saline on hemodynamics, serum atrial natriuretic peptide (ANP), syndecan-1 (marker of endothelial glycocalyx shedding), and extravascular lung water index (ELWI) following hemorrhagic shock.METHODS:Eleven male piglets (Sus scrofa) underwent blood drawing to create 20% drop in mean arterial pressure (MAP). Two-phase resuscitation was performed: Phase 1 using normal saline of an equal volume of blood drawn to create shock and Phase 2 using 40 ml/kg BW of normal saline to simulate hypervolemia and hemodilution. Heart rate, MAP, cardiac index (CI), systemic vascular resistance index, oxygen delivery (DO2), global end-diastolic volume index, ELWI, hemoglobin (Hb), lactate, ANP, and syndecan-1 at each phase and up to 60 min following Phase 2 resuscitation were recorded.RESULTS:Phase 2 resuscitation significantly decreased Hb concentration (P = 0.006), however, DO2 was maintained (P = 1.000). CI increased from shock to Phase 1 (P = 0.029) and further increase in Phase 2 resuscitation (P = 0.001). Overall, there was a transient increase of ANP following Phase 1 resuscitation, from 85.20 ± 40.86 ng/L at baseline to 106.42 ± 33.71 ng/L (P = 0.260). Serum syndecan-1 and ELWI change at all phases were not significant.CONCLUSIONS:We demonstrate compensatory protective mechanism despite overzealous fluid resuscitation. Compensatory increased CI despite decreased Hb maintained DO2. In the absence of inflammation, serum ANP did not increase significantly, no glycocalyx shedding occurred, subsequently no change in ELWI. We show that factors other than volume overload are more dominant in causing glycocalyx shedding.

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.

Cardioprotective Effect of Stem-Leaf Saponins From Panax notoginseng on Mice With Sleep Derivation by Inhibiting Abnormal Autophagy Through PI3K/Akt/mTOR Pathway.

Sleep deprivation (SD) may lead to serious myocardial injury in cardiovascular diseases. Saponins extracted from the roots of Panax notoginseng, a traditional Chinese medicine beneficial to blood circulation and hemostasis, are the main bioactive components exerting cardiovascular protection in the treatment of heart disorders, such as arrhythmia, ischemia and reperfusion injury, and cardiac hypertrophy. This study aimed to explore the protective effect of stem-leaf saponins from Panax notoginseng (SLSP) on myocardial injury in SD mice. SD was induced by a modified multi-platform method. Cardiac morphological changes were assessed by hematoxylin and eosin (H&E) staining. Heart rate and ejection fraction were detected by specific instruments. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of autophagy and apoptosis in heart tissue of SD mice. In vitro, rat H9c2 cells pretreated with rapamycin and the effect of SLSP were explored by acridine orange staining, transient transfection, flow cytometry, and Western blotting analysis. SLSP prevented myocardial injury, such as morphological damage, accumulation of autophagosomes in heart tissue, abnormal high heart rate, serum ANP, and serum LDH induced by SD. In addition, it reversed the expressions of proteins involved in the autophagy and apoptosis and activated PI3K/Akt/mTOR signaling pathway that is disturbed by SD. On H9c2 cells induced by rapamycin, SLSP could markedly resume the abnormal autophagy and apoptosis. Collectively, SLSP attenuated excessive autophagy and apoptosis in myocardial cells in heart tissue induced by SD, which might be acted through activating PI3K/Akt/mTOR signaling pathway.

Neurohormonal responses to oscillatory lower body negative pressure in healthy subjects

Lower body negative pressure (LBNP) has been employed in multiple countermeasure protocols against post spaceflight orthostatic hypotension. However, protocols utilizing oscillatory LBNP (oLBNP) have not been explored in this regard. oLBNP has shown promise in few studies to have good tolerance in conditions of hypovolemic stress and since the negative suction is only phasic, the extravascular fluid shifts associated with negative suction are also hypothesized to be less. Our study addressed the paucity of information on oLBNP by investigating the cardiovascular and neurohormonal effects of oLBNP of −15 and −45 mm Hg in 40 healthy adult males (mean age = 29.6 ± 4.7 years, BMI = 25.1 ± 3.6 kg/m2). After supine rest of 10 min (baseline), oLBNP was applied at −15 mm Hg and −45 mm Hg for 10 min each with a gap of 10 min. Blood sample for neurohormonal analysis was collected at the end of baseline and after each oLBNP exposure. Blood pressure, heart rate, respiratory rate and end tidal CO2 (EtCO2) were recorded for the entire duration. Serum angiotensin II (ATII), antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were analyzed using ELISA. On comparison with the baseline [SBP: 114 ± 2.38, MBP: 75.8 ± 2.16 mm Hg] there was a significant fall in SBP on application of −15 mm Hg as well as −45 mm Hg oLBNP[-15 oLBNP: 107.4 ± 2.34 mm Hg; −45 oLBNP: 105.3 ± 2.28 mm Hg], while there was no significant difference observed in the DBP. There was a significant increase in the heart rate at both −15 [77.29(72.75–85.65) BPM] and −45 mm Hg [81.29 (73.93–86.09) BPM] oLBNP as compared to the baseline [70.41(64.32–79.80) BPM]. No significant difference in the serum ATII, ADH and ANP after 10 min of application of −15 or −45 mm Hg oLBNP as compared to baseline was observed. In conclusion, oLBNP induced legward pooling of blood causes a fall in the blood pressure which initiates the neural reflex mechanisms, most important being the baroreflex and the cardiopulmonary reflex. However, since there was no significant difference in the serum ATII, ADH and ANP from baseline, this suggests that 10 min oLBNP up to −45 mm Hg results in recruitment of cardiovascular neural reflex response but it does not evoke neurohormonal responses which mediate long term volume changes.

Natriuretic Peptides as a Prognostic Marker for Delirium in Cardiac Surgery-A Pilot Study.

Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood–brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels > 64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3–100) and specificity of 42.9% (17.7–71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0–99.8) and specificity of 42.9% (17.7–71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.

Effects of Aerobic Training and Garlic Extract Consumption on Serum ANP and NT-Pro BNP Levels in Obese Hypertensive Patients

Objectives: This study investigated the effects of an eight-week aerobic exercise program and use of garlic extract on serum atrial natriuretic peptide (ANP) and NT-pro brain natriuretic peptide (BNP) levels in obese hypertensive patients. Methods: A total of 50 male obese hypertensive patients with a mean age of 53 ± 7.6 years were recruited in this study. They were randomly assigned to five groups, including aerobic exercise, garlic extract, aerobic exercise + garlic extract, placebo, and control. The experimental groups were subjected to eight weeks of aerobic exercise (three sessions per week, each session for 35 - 60 min with a maximum heart rate of 50% - 70%) and/or garlic extract supplement (6 g daily). Blood samples were collected before interventions and 48 h after the last exercise session. Statistical analysis of data was performed by dependent t-test and Analysis of Covariance (ANCOVA). Results: Body weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, and NT-pro BNP in aerobic exercise, garlic extract, and garlic extract + aerobic exercise reduced significantly compared to control group (P ≤ 0.05). Body weight, BMI, and ANP decreased significantly in aerobic and aerobic + garlic extract groups compared to garlic group (P ≤ 0.001). Moreover, ANP reduced more significantly in aerobic exercise + garlic extract group than in aerobic exercise group (P ≤ 0.05). In addition, NT-pro BNP decreased more significantly in aerobic exercise + garlic extract group than in garlic extract group (P ≤ 0.01). Conclusions: It seems that both aerobic exercise and garlic extract are able to decrease obesity and hypertension. However, their simultaneous use has no additional effects on hypertension control although it influences the body composition and natriuretic peptides.

Sinomenine's protective role and mechanism in stress load-induced heart failure.

This study is designed to investigate the effects and mechanisms of sinomenine (Sin) in stress load-induced heart failure in mice. We used aortic constriction (AB) to cause pressure overload as our heart failure model. Sin was received in mice as the treatment group. Cardiac function and structural changes were detected using echocardiography. Heart-lung mass ratios were measured. The serum levels of IL-10 and IL-17 proteins were detected by using ELISA, cardiac hypertrophy markers atrial natriuretic peptide (ANP), myocardial I and III collagen mRNA levels were detected by RT-PCR. Myocardial type I and III collagen protein levels were detected by Western blotting. Sin significantly improved stress load-induced heart failure (P<0.05), reduced the heart-lung mass ratio, ANP, collagen-I and -III mRNA and protein levels (P<0.05); Sin can enhance the ratio of IL-10/IL-17. Sin may be a promising drug target to improve heart failure. Its role is related to reduce serum ANP levels, inhibit the mRNA and protein level of type I and III collagen and enhance the ratio of IL-10/IL-17.

Associations among NPPA gene polymorphisms, serum ANP levels, and hypertension in the Chinese Han population.

The natriuretic peptide system plays an important role in regulation of blood pressure. The purpose of this study was to comprehensively examine the associations among NPPA gene SNPs, serum atrial natriuretic peptide (ANP) levels, and hypertension. In 736 new-onset hypertensive cases and 736 age- and sex-matched controls, we measured concentrations of serum NT-proANP and genotyped 3 tag-SNPs in NPPA. Serum ANP levels were significantly lower in hypertensive patients than in controls (Wilcoxon two sample test P = 0.011). The difference was also significant in male (P = 0.0161) and female subgroups (P = 0.0011). Compared with the reference group, participants with the highest quartile of ANP levels had a significant decreased risk of hypertension (odds ratio = 0.56, P = 0.0006). The nonsynonymous SNP rs5063 (p.Val32Met) seemed to be associated with ANP levels (P = 0.0209). eQTL analysis found that rs198358 was associated with NPPA gene expression in testis (1.66 × 10-9) and whole blood (4.58 × 10-52). The findings suggested that a common NPPA SNPs rs5063 was associated with serum ANP levels and ANP was prospectively associated with hypertension in the Chinese Han population.

The relationship between atrial natriuretic peptide and microvascular complications of diabetes

Objective: In this study, we aimed to determine the relationship between the atrial natriuretic peptide and microvascular complications of diabetes. Methods: Sixty patients with type 2 diabetes mellitus were enrolled into the study. Patients with a chronic disease other than diabetes mellitus were excluded from the study. The body-mass index, waist circumference, and hip circumference were measured and blood samples for routine biochemical tests were taken after at least 12 hours fasting. The microvascular complications of the patients were evaluated. Results: Thirty-two of the patients had microvascular complications whereas 28 of them did not. Age, body mass index, waist and hip circumference, and atrial natriuretic peptide levels were significantly higher in the group with microvascular complications than those without complications. There was no significant difference in parameters like; waist-hip ratio, blood glucose, HbA1c, fasting insulin, fasting HOMA, sodium, potassium, magnesium, calcium and lipid levels between the two groups. When the relationship between atrial natriuretic peptide and obesity, retinopathy, neuropathy, nephropathy, duration of diabetes, HbA1c, and sex are evaluated separately, the only significant parameters related to atrial natriuretic peptide were the body-mass index, waist circumference, hip circumference measurements, and neuropathy. Conclusions: Positive correlations between serum atrial natriuretic peptide levels and body-mass index, waist circumference, and hip circumference measurements were determined. Also, serum atrial natriuretic peptide levels were significantly higher in patients with obesity or neuropathy than those without obesity or neuropathy.

Roles of apoptosis and inflammation in a rat model of acute lung injury induced right ventricular dysfunction.

The effect of intratracheal lipopolysaccharide (LPS) instillation on right ventricular dysfunction in rats was studied with the aim of exploring underlying mechanisms. A single dose of LPS (10 mg/kg) or an equal volume of saline was instilled intratracheally and lung injury evaluated using histopathologic scoring and wet/dry (W/D) weight ratio at 6 or 12 h post-administration. Besides, serum atrial natriuretic peptide (ANP) was detected using an enzyme-linked immunosorbent assay (ELISA) and right ventricle β-myosin heavy chain (β-MHC) presence was examined using reverse transcription polymerase chain reaction (RT-PCR). Echocardiography examined pulmonary artery acceleration time (PAAT), right ventricular free wall thickness (RVFWT), tricuspid annular plane systolic excursion (TAPSE), and right ventricular end-diastolic diameter (RVEDD). In addition, right ventricular TUNEL staining and Western blots of Bax and Bcl-2 were performed. Right ventricle and left ventricle caspases-3, -8, and -9 activity were examined using fluorometric assay. Finally, right ventricle myeloperoxidase (MPO) neutrophil staining, and right ventricle and plasma cytokines TNF-α, IL-1β, IL-6 detection was performed. Histopathologic lung injury and increased W/D weight ratio was seen at 6 h after LPS intratracheal instillation, along with increased ANP, but not β-MHC. Pulmonary hypertension was indicated by decreased PAAT at 6 h post-exposure. Right ventricular systolic dysfunction and dilation were observed at 12 h post-exposure, as indicated by a significant decrease of TAPSE and increase of RVEDD. Of note, the procedure led to an increased right ventricle TUNEL positive cardiomyocytes, an increased Bax/Bcl-2 ratio, and increased right and left ventricle caspases-3, -8, and -9 activity as early as 6 h post-exposure, which was paralleled by increased right ventricle MPO staining and increased expression of right ventricle and serum cytokines TNF-α, IL-1β, and IL-6. As well as acute lung injury, a single dose of LPS intratracheally instilled can induce pulmonary hypertension at 6 h post-exposure, with obvious right ventricular systolic dysfunction and right ventricular dilation present at 12 h post-exposure, possibly via cardiomyocytes apoptosis and inflammation.