ANP Concentrations Research Articles

A novel mouse model of systemic hypertension by neprilysin overexpression in myeloid cells

There have been many hypertension mouse models created by transgenesis. The transgenesis technologies to create hypertensive mouse models mostly target the renin-angiotensin system (RAS). Here, we show that enhanced expression of neprilysin driven by the myeloid-specific c-fms promoter causes systemic hypertension in mice. [Method] Transgenic mice, termed Nep mice, were created with a construct containing the c-fms promoter and the neprilysin gene (MME). Blood pressure was measured by tail-cuff. Circulating vasoactive substances were analyzed by ELISAs. [Results] Nep mice showed higher systolic blood pressure compared with WT mice (117.0±1.75 vs. 107.1±2.373 mmHg, p=0.0018). The sodium concentration in a 24hr urine was significantly lower in Nep mice (0.2093±0.0039 vs. 0.2445±0.0054 μmol/μl urine, p=0.0004). The concentration of circulating neprilysin was significantly higher in Nep mice (3085±750.5 vs. 1098±197.1 pg/ml, p=0.0283). Notably, the plasma concentration of ANP showed no significant difference between Nep and WT mice although hypertension usually causes an ANP increase. [Conclusion] Overexpression of neprilysin in monocytes causes systemic hypertension associated with sodium and water retention. These mice might be useful for studying the pathologies of heart diseases and hypertension due to volume overload, and in addition, other neprilysin related diseases like Alzheimer’s disease to investigate the interaction with immune cells and beta-amyloid which is cleaved by neprilysin. NIH R01 AI164519 (KEB, P.I.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Associations of atrial natriuretic peptide with measures of insulin and adipose depots.

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

PS-B02-6: CHANGES OF THE EXTRACELLULAR MATRIX AND INTERCELLULAR COMMUNICATION IN THE RAT HEARTS WITH VOLUME-PRESSURE OVERLOAD AND MODULATION BY CARDIOPROTECTIVE DRUGS

Objective: Pathogenesis of heart failure (HF) and hypertension with a focus on extracellular matrix (ECM) and communication in the heart is still a current scientific topic that calls for new findings. Design and method: We used as experimental model normotensive (HSD) and hypertensive (TGR) rats with aortocaval fistula (ACF) supplemented with an ACE inhibitor (ACEi)(15weeks, 6 mg/L) and an AT1 receptor blocker (ARB)(15weeks, 200 mg/L). At the end of the experiments, serum and myocardial tissue samples of the right and left ventricles were taken for biometric, biochemical, gene, protein and microscopic analyzes. Results: We observed an increase in the cardiac weight index after ACF, left and right ventricles in HSD and TGR rats. ACEi and ARB have normalized this condition to a greater extent. Due to ACF, serum concentrations of ANP and TBARS were increased in the blood serum of both strains. ACF increased hydroxyproline levels in right ventricular levels in HSD and TGR rats and left ventricular TBARS in TGR rats. In addition, ACF increased mRNA collagenI, and collagenI protein expression in the left and right ventricles of HSD rats. In contrast, ACF reduced Cx43 and pCx43 protein levels in the left and right ventricles of both strains, SMAD2 expression in the right ventricle in HSD and TGR rats. ACF also suppressed MMP-2 protein expression in both cardiac ventricles in HSD rats and PKCepsilon protein expression in both heart chambers of both strains. Hypertension caused a slight decrease in the protein expression of Cx43, pCx43 and PKCepsilon and an increase in the expression of PKCdelta in cardiac ventricles of both rat strain. Hypertension further increased and collagenI in TGR rats in the left and right ventricles of the heart. Microscopic analyzes showed that ACF induced cardiomyocyte hypertrophy as well as decreased activity of enzymes involved in ACF energy metabolism. An interesting finding was that the signaling pathways involved in cardiac remodeling were more normalized by the ARB, while proteins involved in intercellular communication by ACEi. Conclusions: Based on the results obtained from the experiment, it can be stated that the right ventricle is more significantly affected by ACF and the results of analyzes in TGR indicate adaptation, attenuated responses to the parameters we observed. Supported by: APVV-21-410, VEGA-2/0158/19.

Measurement of ANP, BNP and endothelin‐1 concentrations in jumping horses with heart valvular regurgitation and their correlation with the dimensions of heart structures

SummaryBackgroundNatriuretic peptides and endothelin‐1 are used as biochemical biomarkers for the diagnosis and prognosis of heart diseases.ObjectivesThis study aimed to investigate plasma ANP, BNP and endothelin‐1 in jumping horses with various manifestations of heart valve regurgitation and their association with echocardiographic variables.Study designClinical evaluations including cardiac auscultation were performed in 198 jumping horses, and 30 horses were chosen.MethodsSixteen jumping horses with murmurs of grade 3/6 to 5/6 having various degrees of heart valve regurgitation with the severity of insignificant to moderate on colour Doppler echocardiography were considered as the valvular regurgitation group (average age 9.75 ± 3.28 years and weight 427.43 ± 82.22 kg, and consisting of 10 mares, three stallions and three castrated male horses with breeds of 12 Thoroughbred and four crossbred). Fourteen healthy horses were chosen as the healthy group (average age 8.64 ± 2.44 years and weight 462.14 ± 77.42 kg, and consisting of nine mares, three stallions and two castrated males with breeds of 12 Thoroughbreds, and two crossbred). Blood samples were collected from the jugular vein, and plasma concentration of ANP, BNP and endothelin‐1 was determined using Sandwich ELISA by a horse‐specific kit. Then, the plasma concentration of mentioned peptides and echocardiographic variables were compared between the two groups.ResultsB‐type natriuretic peptide was significantly increased in horses with valve regurgitation compared to healthy horses, but increases in ANP and endothelin‐1 were insignificant. Also, in the valvular regurgitation group, horses with a pulmonic valve disorder had a significantly higher concentration of BNP and endothelin‐1 than healthy horses. Assessment of the relation between ANP, BNP and endothelin‐1 with echocardiographic variables showed a significant correlation between ANP and right ventricle length (RVL) and left ventricle width (LVW) in systole and endothelin‐1 with right ventricle width (RVW) and left ventricle width in systole, but BNP had no significant correlation.Conclusion and clinical importanceAccording to the study results, it can be assumed that the measurement of these cardiac biomarkers can be helpful in the diagnosis of the jumping horse with cardiac valvular disorders (especially pulmonic valve regurgitation) and changes in the dimensions of the heart ventricle.

Amelioration of Hypertension by Oryeongsan through Improvements of Body Fluid and Sodium Balance: Roles of the Renin-Angiotensin System and Atrial Natriuretic Peptide System.

Oryeongsan (Wulingsan in China and Goreisan in Japan), a formula composed of five herbal medicines, has long been used for the treatment of imbalance of the body fluid homeostasis in Asian countries. However, the mechanism by which Oryeongsan (ORS) improves the impaired body fluid and salt metabolism is not clearly defined. The present study was performed to define the role of the cardiorenal humoral system in the ORS-induced changes in blood pressure and renal function in hypertension. Experiments were performed in normotensive and two-kidney, one-clip hypertensive rats. Changes in the fluid and salt balance were measured in rats individually housed in metabolic cages. Changes in the systemic and local renin-angiotensin system (RAS) and cardiac natriuretic peptide hormone system (NPS) were evaluated. ORS water extract was administered by oral gavage (100 mg/kg daily) for 3 weeks. ORS induced diuresis and natriuresis along with an increase in glomerular filtration rate and downregulation of the Na+/H+ exchanger 3 (NHE3) and aquaporin 2 expression in the renal cortex and medulla, respectively. Furthermore, treatment with ORS significantly decreased systolic blood pressure with contraction of body sodium and water accumulation in hypertensive rats. ORS-induced changes were accompanied by modulation of the RAS and NPS, downregulation of the systemic RAS and cardiorenal expression of angiotensin-converting enzyme (ACE) and angiotensin II subtype 1 (AT1) receptor, and upregulation of the plasma ANP concentration and cardiorenal expression of ANP, ACE2, Mas receptor, and AT2 receptor. These findings indicate that ORS induces beneficial effects on the high blood pressure through modulation of the RAS and NPS of the cardiorenal system, suppression of the prohypertensive ACE-AT1 receptor pathway and NHE3, accentuation of the antihypertensive ACE2-Mas axis/AT2 receptor pathway in the kidney, suppression of the systemic RAS, and elevation of the plasma ANP levels and its synthesis in the heart. The present study provides a biological basis for the use of ORS in the treatment of impaired volume and pressure homeostasis.

Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes.

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477pg/mL (-6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83pg/mL (-43.4%), P < 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P < 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

Oryeongsan (Wulingsan) ameliorates impaired ANP secretion of atria from spontaneously hypertensive rats

Oryeongsan (ORS), a herbal medicine formula, has long been used for the treatment of impaired body water balance in Asian countries. Recently, it was shown that ORS administration modulates the renin-angiotensin system (RAS). Purpose of the present study was to determine characteristics of atrial ANP secretion and effects of ORS on the secretion in the atria from spontaneously hypertensive rats (SHR). Normotensive WKY groups (WKY-V, WKY-ORS, WKY-LOS) and hypertensive SHR groups (SHR-V, SHR-ORS, SHR-LOS) treated with vehicle, ORS, and losartan as a positive control group, respectively, were used. Experiments were performed in perfused beating atria (1.3 Hz) allowing atrial distension, acetylcholine (ACh) stimulation, and serial collection of atrial perfusates. The secreted ANP concentration was measured using radioimmunoassay. Interstitial fluid (ISF) translocation was measured using [3H]inulin clearance. Stepwise increase in atrial distension by 1.1, 2.0, and 2.7 cmH2O above basal distension further increased ANP secretion proportionally in the atria from WKY-V, but the response was significantly suppressed in the atria from SHR-V. Cardiomyocyte ANP release, the first step of atrial ANP secretion, was suppressed in the atria from SHR-V compared to those from WKY-V (−8.02 ± 2.86, −15.86 ± 2.27, and −20.09 ± 3.62%; n = 8, for SHR-V vs. 8.59 ± 2.81, 15.65 ± 7.14, and 38.12 ± 8.28%; n = 8, for WKY-V; p < 0.001 for all stepwise distension, respectively). Chronic treatment with ORS reversed the suppressed ANP release in atria from SHR-ORS group (6.76 ± 3.92, 9.12 ± 2.85, and 28.79 ± 1.79% for SHR-ORS; n = 5 vs. SHR-V; n = 8; p = 0.01, p < 0.001, p < 0.001, respectively). The effects of ORS were comparable to those of losartan. Trans-endocardial translocation of ISF, the second step of atrial ANP secretion was similar in the atria from the hypertensive SHR-V and normotensive WKY-V. ACh-induced ANP secretion and cardiomyocyte ANP release were also suppressed in the atria from SHR-V compared to WKY-V and ORS reversed the suppression. These findings were accompanied with accentuation of the AT1 receptor expression and suppression of the AT2/Mas receptor, M2 mACh receptor and GIRK4, a molecular component of KACh channel, expression in the atria from SHR-V. Further, treatment with ORS or losartan reversed the expressions in the groups of SHR-ORS and SHR-LOS. These results show that ANP secretion is suppressed in the atria from SHR in association with accentuation of AT1 receptor and suppression of AT2/Mas receptor and KACh channel expression. Treatment with ORS ameliorates impaired ANP secretion through improving cardiomyocyte ANP release with modulation of the cardiac RAS and muscarinic signaling. These findings provide experimental evidence which supports the effect of ORS on the regulation of atrial ANP secretion in the atria from SHR.

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.

Study Effects of Nigella Sativa Seeds Oil in Some Physiological Parameters in Experimental Heart Failure Induced by Ivabradine in Male Rats

Aim of this study was to investigate the effects of Nigella Sativa Seeds oil In some physiological parameters&#x0D; against heart failure Induced By Ivabradine in rats .A total of 60 male rats were used in this experiment, the&#x0D; rats were divided into three groups: control rats (n = 20); IBD (n = 20); IBD+ N. sativa oil (n = 20). The&#x0D; first group (G1) was a control group. The second group (G2) was given 10 mg/kg of IBD, while the third&#x0D; group (G3) was injected with 10 mg/kgIBD + oral dosage of 2.5 mg/kg N. sativa oil for three months., after&#x0D; three months, the blood was withdrawn from the heart. to measure the concentration of ANP, BNP, NE,&#x0D; A-II, ALDO, ACE, MDA, SOD, TNF-? and IL-6 the Results revels that Levels of BNP, NE, MDA, IL-6&#x0D; and TNF-?. were significantly increasead in G2 rats, with no significant difference was observed in ANP&#x0D; in rats in G2 compared to G1 rats . The level of ACE, A-II, SOD and ALDO in G2 rats had significantly&#x0D; decreased compared to that observed in G1 rats, oral administration of Nigella Sativa seeds oil (G3) showed&#x0D; no significant difference inANP, BNP, NE, A-II, ALDO, ACE, MDA, SOD, TNF-? and IL-6 compared with&#x0D; G1 group.

Effects of atrial natriuretic peptide on mitochondria function in cortical collecting duct cells

BackgroundAtrial natriuretic peptide (ANP) is a hormone released from cardiomyocytes in response to cardiac wall stretching. ANP acts on the kidney by promoting sodium and water excretion as well as providing a general vasodilatory effect. Direct application of ANP has been shown to reduce sodium reabsorption in the renal tubular cells. Recently, it has been discovered that natriuretic peptides (NPs) are involved in lipolysis, lipid oxidation, and mitochondrial respiration. Evidence of a correlation between the activity of the NP system and mitochondrial respiration and biogenesis has been explored to some extent; however, little is known about these pathways in the kidney. Here we hypothesized that ANP may be implicated in mitochondrial uncoupling in the cortical collecting ducts (CCD), affecting sodium transport in this segment.MethodsMouse cortical collecting duct (mpkCCD) cells were cultured in DMEM/F12 medium with supplements and grown on glass‐bottom dishes, 96‐well plates or permeable supports. Cells were treated with ANP (5 nM to 10 μM range) for 1 or 24 hours. Fluorescent dyes TMRM and Rhod123, CellRox Deep Red, AmplexRed, Rhod2 and Hoechst 33342 were used to label mitochondrial membrane potential (TMRM/Rhod123), production of mitochondrial ROS, hydrogen peroxide, calcium, and nuclei in live cells, respectively. A Leica TCS SP5 confocal microscope or a BMG Labtech microplate reader were employed to monitor fluorescence intensity changes in response to ANP. Mitochondrial stress test assays were performed using a Seahorse XF96 Extracellular Flux Analyzer. Sodium currents in the polarized mpkCCD monolayers were measured with an EVOM multimeter. One‐way ANOVA (OriginPro) was used for statistical comparisons.ResultsFluorescence microscopy with TMRM showed a mild (~30% at maximum effect) dose‐dependent decrease in mitochondrial membrane potential in mpkCCD cells treated with low dose ANP for 1, 2 and 24 h (1 nM to 500 nM), which was, interestingly, attenuated by higher ANP concentrations (&gt;5 μM). These data were confirmed in a 96‐well plate assay using Rhod 123 (1 h and 24 hours). In addition, we observed an acute increase in ROS (and specifically, hydrogen peroxide) production and mitochondrial Ca2+ level in response to ANP (at 1 h), which is in line with the mild uncoupling reported above. Preliminary seahorse analysis indicated that ANP decreases mitochondrial respiration in these cells in a dose‐dependent manner. We have also shown that direct uncoupling of mitochondria with FCCP results in a dose‐dependent decrease in sodium currents mediated by Epithelial Sodium Channel (ENaC) as measured in short circuit current experiments.ConclusionDecreased mitochondrial membrane potential is indicative of a disruption in the oxidative phosphorylation, which is the main mechanism of ATP synthesis in the cell and the source of energy for Na+/K+‐ATPase (NKA). Since NKA provides the gradient for Na+ reabsorption in CCD, the reported mitochondria‐mediated effect suggests a novel pathway through which ANP may regulate Na+ reabsorption in the collecting ducts, potentially affecting blood pressure.Support or Funding InformationAPS Summer Undergraduate Fellowship Program; NIH R00 DK105160, Dialysis Clinic Inc Reserve Funds.

Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling

BackgroundInformation on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival.MethodsWistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL – fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF – fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations.ResultsBefore surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 μm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and β-myosin heavy chain did not differ between groups.ConclusionIntermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Endothelin-1 (ET-1), N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP), and tumour necrosis factor alpha (TNF-α) in children with primary hypertension and hypertension of renal origin.

Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children. We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests. ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046). The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.

Historical Pollution of an Urban Watershed Based in Geochemical, Geoacumulation, and EROD Activity in PLHC-1 Analyses in Sediment Cores.

In the present study, the environmental changes over the past 100years in the Cambé River watershed in Southern Brazil were investigated. For this, a sediment core was collected to examine the distribution of metals, polycyclic aromatic hydrocarbons (PAHs), and ecotoxicological markers. The core corresponds from 1914 to 2012, which was obtained by the decay of 210Pb. Changes in the study area also were examined by: Geoaccumulation index (Igeo) and enrichment factor (EF), sediment quality guidelines (SGQs), and ethoxyresorufin-O-deethylase (EROD) activity in Poeciliopsis lucida hepatocellular carcinoma (PLHC-1) cells line. The Σ16 PAHs ranged from 242.6 to 40,775ngg-1, with pyrogenic source at the beginning of the core, which likely corresponds to the burning of forests to establish the city and the later use of fossil fuels from 1960 to 2012. In the 1930s, most of metals presented a concentration below the background. After the 1930s, high concentrations can be associated with the intense use of fertilizers (Cd, Cu, Zn, Hg) and increases in urban traffic (Zn and Pb). Igeo showed that the distribution of Cu is considered moderately to strongly polluted, and the EF of Pb was considered as moderately polluted. Statistical analyses showed a strong relation between the presence of the ANP, FLU, PHE, BaP, IND, and Bghi compounds and the induction of EROD activity, and no correlation with heavy metals. A prediction model for the linear regression was obtained between the ANP and BaP concentrations and the EROD activity, with an accuracy of 99%.

PL - 021 The research of High temperature exercise under different humidity environment effect on the body of water and salt metabolism

Objective Objective: This study was to investigate the body under high temperature (33 ℃) with different relative humidity (80%, 50%, 20%) combination of environment, respectively for 20 min 60% VO2max individual strength of quiet before and after the exposure of movement and under the same conditions, by measuring the participants within the body weight, serum sex hormone of blood, blood Na+、K+, Na+、K+ concentration in the urine of change, to explore in the sports stress and thermal stress of two kinds of stimulating the body water and salt metabolism characteristics, and to explore the effects of environmental humidity on the body's homeostasis.&#x0D; Methods Methods: This study selected 12 students of sports training major from Beijing sports university as subjects, with themselves as the control. The experiment is divided into six categories, respectively: high temperature 33℃ and 20% RH exposure group, the high temperature 33℃ and 20% RH campaign group, high temperature 33℃and 50% RH exposure group, the high temperature 33℃ and 50% RH campaign group, high temperature 33℃ and 80% RH exposure group and high temperature 33℃ and 80% RH. In this study all the environmental temperature are set up to 33℃, exercise intensity level of 60% VO2max selection for individual participants. Before every experiment, all participants were asked to quiet sit for 20 min and then measure the subjects' body weight, charge the subjects' vein blood and urine, take the same operation immediately after the experiment. Blood samples were stored at room temperature for 1 h, and 3000r/min was centrifuged for 20min. Serums were gathered through centrifugation, The urine and Serums were partial shipments in tube to be indicators of measurement. Serum Renin、ANGII、ALD、ADH、ANP、Na+、K+ concentration of serum and urine were tested&#x0D; Results Results: (1)The subjects' weight loss percentage of exercise group was obviously higher than that of quiet exposure group, the difference is statistically significant (P &lt; 0.01); In 80% RH environment weight loss percentage is significantly higher than that of 50% RH and 20% RH values (P &lt; 0.01).There is no difference between 20%RH and 50%RH. (2) The exercise group of Renin, ANGII, ALD, ADH, concentration is significantly higher than the value of exposed group (P &lt; 0.01), but the ANP concentrations were significantly lower than pure quiet exposure levels (P &lt; 0.01).&#x0D; Conclusions Conclusions: (1) The body sweat more after exercise than just quiet exposed in high temperature, weight loss phenomenon more obvious; And with the increase of relative humidity environment, dehydration will more serious. (2) Exercise factors can significantly promote the release of blood Renin, ANGII, ALD, ADH and inhibit the release of ANP in the blood. By the way of strengthening the absorption process of water and ions, it can maintain the body's balance of water and ions.

The Effect of Bariatric Surgery on Neprilysin and Vasoactive Factors

Objective: Since morbid obesity is associated with congestive cardiac failure and hypertension, and gastric bypass surgery is followed by a reduction in blood pressure and a reduction in the risk of congestive cardiac failure, we hypothesized that weight loss following bariatric surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of renin angiotensin system, catecholamines and endothelin-1 with an increase in the concentrations of vasodilators. Method: Fasting blood samples were obtained from fourteen patients with morbid obesity and diabetes prior to and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Plasma and serum were separated for the measurement of neprilysin; vasoconstrictors, angiotensinogen, renin, angiotensin II, endothelin-1, epinephrine and norepinephrine; and vasodilators, ANP, BNP, cGMP, and cAMP. The mRNA expression of angiotensin converting enzyme (ACE) and adenylate and guanylate cyclases in circulating mononuclear cells (MNC) was also measured. Results: Six months after RYGB, BMI fell from 52.1±4.8 to 40.4±4.0 kg/m2 and there were significant improvements in the HbA1c. Plasma concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27±16%, 22±10% 22±8%, 35±13% and 17±6% (p&amp;lt;0.for all) respectively, while ANP concentrations increased significantly by 24±13% at 6 month following surgery. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations and ACE mRNA expression. Conclusion: RYGB suppressed neprilysin concentrations, which may contribute the observed increase in plasma ANP concentrations. In addition, RYGB resulted in a reduction in plasma angiotensinogen, angiotensin II, renin and endothelin-1 concentrations. These changes may contribute to the reduction in the risk of congestive cardiac failure and blood pressure after RYGB. Disclosure P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. H. Ghanim: None. S. Monte: Stock/Shareholder; Self; Mobile Pharmacy Solutions (Community Pharmacy). Employee; Self; Synergy Bariatrics, a Department of ECMC. K. Green: None. J.A. Caruana: None.

Decreases in neprilysin and vasoconstrictors and increases in vasodilators following bariatric surgery

The aim of this study was to determine if weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of the renin angiotensin system (RAS), catecholamines and endothelin-1, and also with an increase in the concentrations of vasodilators. Fasting blood samples were obtained from 15 patients with morbid obesity and diabetes prior to and 6 months after RYGB surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and the mRNA expression of related genes in circulating mononuclear cells (MNC) were measured. Six months after RYGB surgery the concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27 ±16%, 22 ±10%, 22 ±8%, 35 ±13% and 17 ±6% (P < .05 for all), respectively, while ANP concentrations increased significantly by 24 ±13%. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations, or angiotensin converting enzyme (ACE) expression. These changes may contribute to the reduction of congestive cardiac failure and blood pressure risks after RYGB surgery.

Neprilysin inhibition and endothelin-1 elevation: Focus on the kidney

Increasing the degree of renin-angiotensin system (RAS) blockade by combining ≥2 RAS blockers marginally increases efficacy, but results in more side effects. Hence, interference with other systems is currently being investigated, like potentiation of natriuretic peptides with neprilysin inhibitors. However, the neprilysin inhibitor thiorphan was recently found to increase endothelin-1 when administered to TGR(mREN2)27 (Ren2) rats on top of RAS blockade. Here we investigated whether this effect is thiorphan-specific, by comparing the neprilysin inhibitors thiorphan and sacubitril, administered by osmotic minipumps at a low or high dose for 7 days, in Ren2 rats. Plasma and urinary levels of endothelin-1, atrial and brain natriuretic peptide (ANP, BNP) and their second messenger cyclic guanosine 3′5′ monophosphate (cGMP) were monitored. No significant differences were found in the plasma concentrations of endothelin-1, cGMP, ANP and BNP after treatment, although plasma ANP tended to be higher in the high-dose thiorphan treatment group and the low- and high-dose sacubitril treatment groups, compared with vehicle. Urinary endothelin-1 increased in the low-dose thiorphan and high-dose sacubitril groups, compared with baseline, although significance was reached for the former only. Urinary cGMP rose significantly in the high-dose sacubitril treatment group compared with baseline. Both urinary endothelin-1 and cGMP were significantly higher in the high-dose sacubitril group compared with the low-dose sacubitril group. In conclusion, endothelin-1 upregulation occurs with both thiorphan and sacubitril, and is particularly apparent in neprilysin-rich organs like the kidney. High renal neprilysin levels most likely also explain why sacubitril increased cGMP in urine only.

Polyphenol rich ethanolic extract from Boerhavia diffusa L. mitigates angiotensin II induced cardiac hypertrophy and fibrosis in rats.

Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats. Moreover, Ang II induced myocardial oxidative stress was reduced by BDE which was apparent from diminished level of lipid and protein oxidation products, increased activities of membrane bound ATPases and endogenous antioxidant enzymes along with enhanced translocation of Nrf2 from the cytosol to nucleus. It appears that BDE evokes its antioxidant effects by attenuating lipid peroxidation, enhancing the translocation of Nrf2 from the cytoplasm to nucleus as well as by regulating the metabolism of glutathione. The extent of fibrosis during cardiac hypertrophy was determined by histopathology analysis and the results revealed that BDE treatment considerably reduced the fibrosis in the heart. HPLC analysis of BDE leads to the identification of four compounds viz., quercetin, kaempferol, boeravinone B and caffeic acid. The study substantiate the effect of B. diffusa in protecting the heart from pathological hypertrophy and the attenuation of cardiac abnormalities may be partly attributed through the reduction of oxidative stress and cardiac fibrosis. Since the plant is widely used as a green leafy vegetable, incorporation of this plant in diet may be an alternative way for the prevention and better management of heart diseases and associated complications.

ANP and BNP plasma levels in patients with rheumatic mitral stenosis after percutaneous balloon mitral valvuloplasty.

IntroductionAtrial (ANP) and B-type (BNP) natriuretic peptides are hormones secreted by the heart as a response to volume expansion and pressure overload.AimTo assess the changes of ANP and BNP after percutaneous balloon mitral valvuloplasty (PBMV) and to investigate factors associated with endpoints.Material and methodsThe study included 96 patients (90.7% females, age 51.6 ±12.2 years) with rheumatic mitral valve stenosis (mitral valve area (MVA) 1.18 (1.01–1.33) cm2, mean mitral gradient (MMG) 8.2 (7.1–9.2) mm Hg, NYHA 2.09 (1.9–2.5)). Patients were followed up for 29.1 months for the search of endpoints.ResultsThe PBMV was successful in all cases. After the procedure MVA increased (1.18–1.78 cm2, p < 0.01) and pulmonary capillary wedge pressure (PCWP) decreased (29.8–21.8 mm Hg, p < 0.01). Concentration of ANP significantly rose 30 min after the PBMV (79.2 vs. 134.2 pg/ml, p = 0.012) and dropped significantly after 24 h (134.2 vs. 70.4 pg/ml, p = 0.01). Furthermore, after 36 months concentration of ANP did not differ from the baseline value (p = NS). BNP concentration at day 1 was lower than at baseline (94.5 vs. 80.2 pg/ml, p = 0.032). Moreover, during the follow-up period BNP continued to fall at all time points. In univariate analysis parameters associated with endpoint occurrence were baseline PAP (p = 0.023), baseline PCWP (p = 0.022), baseline NYHA (p = 0.041) and increase in 6-minute walk test (6MWT) (p = 0.043). In multivariate analysis the only factor associated with endpoint occurrence was baseline NYHA (HR = 1.52, 95% CI: –1.3–1.91, p = 0.022).ConclusionsPatients with MS had increased levels of both BNP and ANP. Baseline NYHA class was found to be associated with outcomes after the procedure.