Peritoneal dialysis related eosinophilic peritonitis: a case report and review of the literature.

BACKGROUND: Overt eosinophilic peritonitis (EP) is a relatively uncommon complication of peritoneal dialysis (PD), although not rare. Here we reported a case of EP relieved after changing dialysate.  CASE PRESENTATION: A 28-year old male patient developed cloudy PD effluents within the first month after PD started. Cytological study of PD effluents showed elevated white blood cells and polynuclear cells. Bacteria culture of PD effluents repeated for several times were all negative, and no pathogen was found by metagenomics next generation sequencing (mNGS). Antibiotic therapy for 28-day was ineffective. Based on these and increased eosinophils in peritoneal fluid, he was finally diagnosed as EP. PD dialysate was changed (consists of the same buffer agent and electrolytes, but is packed in bags that do not contain PVC), and the patient's PD effluent became clear. Of note, EP did not relapse 5 months later when the patient started to use the former PD solution again. CONCLUSION: Although PD effluent turbidity almost always represents infectious peritonitis, there are other differential diagnoses including EP. For patients with cloudy fluid accompanied by mild symptoms who do not response to antibiotic therapy, it is reasonable to consider the possibility of this disease. EP tends to heal spontaneously, however, antihistamines or glucocorticoids are required sometimes to avoid catheter obstruction. For patients with no obvious incentives, replacement of dialysate may be useful.

Characteristics of the vaginal microbiomes in prepubertal girls with and without vulvovaginitis.

The present study focused on the characteristics of the vaginal microbiomes in prepubertal girls with and without vulvovaginitis. We collected 24 vaginal samples and 16 fecal samples from 10 girls aged 3-9 years with vulvovaginitis and 16 healthy girls of the same age. The samples were divided into three groups: fecal swabs from healthy controls (HF), vaginal swabs from healthy controls (HVS), and vaginal swabs from girls with vulvovaginitis (VVS). Sequencing of the V3-V4 region of the 16S rDNA gene was performed with the NovaSeq PE250 platform to reveal the vaginal microbial community structure in healthy prepubertal girls and vulvovaginitis-associated microbiota. The intestinal microbiomes of healthy children were also analyzed for comparison. This study revealed that the healthy vaginal tract in prepubertal girls was dominated by Prevotella, Porphyromonas, Ezakiella, and Peptoniphilus species, with a high diversity of microbiota. The vulvovaginitis-associated microbiota were dominated by Streptococcus, Prevotella, Haemophilus, and Granulicatella, with lower diversity than that in healthy girls. Furthermore, the compositions of the vaginal and intestinal microbiomes were completely different. ANOSIM, MRPP, Adonis, and AMOVA were used to analyze the beta diversity, and the results showed that there were significant differences in the microbial communities among the three groups. Lactobacillus deficiency and high bacterial diversity were characteristics of the vaginal microbiome in healthy prepubertal girls; this is inconsistent with that in reproductive-age women. The vulvovaginitis-associated vaginal microbiota differed dramatically from normal microbiota, and the main causative agents were not fecal in origin.

[Mechanism of salicylic acid ameliorates salt-induced changes in Andrographis paniculata].

In this study, Andrographis paniculata seedlings were used as experimental materials to study the effects of salicylic acid(SA) on the growth and effective component accumulation of A. paniculata under NaCl stress. The results showed that with the increase of NaCl concentration, the growth of A. paniculata seedlings was significantly inhibited, and the content of carotene and carotenoid decreased. The activity of antioxidant enzyme was enhanced. At the same time, the contents of proline, proline and soluble protein were on the rise. The contents of andrographolide, new andrographolide and deoxyandrographolide showed an upward trend, while deoxyandrographolide showed a downward trend. Treatment with 100 mmol·L~(-1) NaCl+5 mg·L~(-1) SA showed a significant increase in antioxidant enzyme activity in A. paniculata leaves. Treatment with 100 mmol·L~(-1) NaCl+10 mg·L~(-1) SA showed significant changes in soluble protein and proline content in A. paniculata leaves, while MDA content in A. paniculata leaves significantly decreased. 10 mg·L~(-1) SA had the best effect on the growth of A. paniculata seedlings under salt stress. Under the treatment of 50 mmol·L~(-1) NaCl+10 mg·L~(-1) SA, fresh weight, dry weight and leaf dry weight of A. paniculata seedlings reached the highest level, which were 1.02, 1.09 and 1.11 times of those in the control group, respectively. The concentrations of NaCl and 10 mg·L~(-1) SA were significantly higher than those of the control group. Four key enzyme genes of A. paniculata diterpene lactone synthesis pathway were selected to explore the molecular mechanism of salicylic acid to alleviate salt stress. With the increase of salt stress, the relative expressions of HMGR, GGPS and ApCPS were up-regulated, indicating that salt stress may enhance the synthesis of A. paniculata diterpene lactone through MVA pathway. SA can effectively promote the growth and development of A. paniculata under salt stress, improve its osmotic regulation and antioxidant capacity, improve its salt tolerance, and alleviate the effects of salt stress on A. paniculata.

Administration of losartan improves aortic arterial stiffness and reduces the occurrence of acute coronary syndrome in aged patients with essential hypertension.

BACKGROUNDS AND AIMS: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated. METHODS: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. RESULTS: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long-term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long-term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan. CONCLUSION: Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.

Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats.

Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown.Methods: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days. The expression of miR-133a was determined by fluorescence in situ hybridization. The learning and memory were evaluated by step-down, step-through, and morris water maze (MWM) tests.Results: In streptozotocin-injected rats, hyperglycemia dramatically induced miR-133a ectopic expressions in vascular endothelium, reduced GTPCH1 gene expressions and BH4 levels, which were reversed by berberine administration (1.0 g/kg/day, 8 weeks). Hyperglycemia also inhibited acetylcholine-induced vasorelaxation in middle cerebral artery and reduced blood supply to the brain, which were bypassed by berberine. Ex vivo studies indicated that miR-133a agomirs abolished these beneficial effects of berberine on acetylcholine-induced vasorelaxation, while supplement of L-sepiapterin prevented endothelial dysfunction in middle cerebral artery isolated from rats. By performing step-down, step-through, and MWM tests, we observed that hyperglycemia significantly caused the impairments of learning and memory in streptozotocin-injected rats. Importantly, these aberrant phenotypes in diabetic rats were normalized by berberine therapy. Finally, berberine reduced miR-133a expression, and increased both BH4 levels and NO production in cultured endothelial cells treated with high glucose.Conclusion: Berberine improves vascular dementia in diabetes, which is possibly related to the suppression of miR-133a ectopic expression in endothelial cells.

Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart.

BACKGROUND/AIMS: Neuronostatin, derived from the somatostatin preprohormone, was recently identified to be produced by several tissues exerting a role in cardiovascular regulation and metabolism. Nonetheless, the precise mechanism behind neuronostatin-elicited myocardial responses remains elusive. METHODS: This study was designed to elucidate the impact of neuronostatin on cardiac contractile function and the underlying mechanism of action involved. Adult male C57 BL/6 mice were subjected to a bolus injection of neuronostatin (50 µg/kg, i.p.). Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ handling properties were monitored to evaluate the effect of neuronostatin on cardiac function. Western blot analysis was used to examine potential signaling mechanisms involved. RESULTS: Neuronostatin administration suppressed myocardial and cardiomyocyte contractile function and disturbed intracellular Ca2+ homeostasis. We observed enlarged LVESD (with unchanged LVEDD), reduced fractional shortening, depressed peak shortening, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca2+, and prolonged relengthening duration in hearts from neuronostatin-treated mice. These effects were accompanied by downregulation of phosphorylation of sarcoplasmic reticulum Ca2+- ATPase (SERCA) and phospholamban (PLB) and activation of AMPK. CONCLUSION: Our data suggest that the cardiac depressant properties of neuronostatin possibly associated with loss of SERCA phosphorylation and AMPK activation. These findings revealed a potent inhibitory capacity for neuronostatin on cardiac function, the physiological relevance of which deserves further study.

Predictive Factors of the Entrepreneurial Performance of Undergraduates.

College students have gradually become the main force of entrepreneurship in mass entrepreneurship and innovation. However, their entrepreneurial performance was not as good as expected. We have carried out research to analyze the predictive factors of entrepreneurial performance of college students and put forward targeted suggestions, hoping to be helpful to improve their entrepreneurial performance of them. Based on questionnaire data obtained from 2,097 college student entrepreneurs, this study uses the structural equation model to analyze the predictive factors of the entrepreneurial performance of college students. The survey results of the questionnaire show that both personal and behavioral factors influence the entrepreneurial performance of college students. In this study, personal factors in this study mainly include entrepreneurial willingness, personality, and ability of entrepreneurs. Behavioral factors mainly refer to the positive behaviors of entrepreneurs that can affect entrepreneurial performance.

Tanshinone IIA attenuates peritoneal fibrosis through inhibition of fibrogenic growth factors expression in peritoneum in a peritoneal dialysis rat model.

BACKGROUND: Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and is the main cause of dialysis inadequacy and PD withdrawal. It has been reported that Tanshinone IIA can ameliorate fibrosis in various tissues. In this report, we investigate the effects of Tanshinone IIA on peritoneal fibrosis in an animal model. METHODS: Forty rats were randomly divided into four groups (n = 10 per group) that received daily intraperitoneal injection of saline, 4.25% glucose-based peritoneal dialysis fluid (PDF), or PDF along with 50 or 100 mg/L Tanshinone IIA. Eight weeks later, the rats were sacrificed and peritoneal tissue samples were collected for analysis. The expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) in parietal peritoneum was examined by immunohistochemistry. The mRNA and protein expression of TGF-ß1 and CTGF in omentum was examined by reverse transcription polymerase chain reaction or Western blot. RESULTS: Tanshinone IIA significantly suppressed submesothelial compact zone thickening and matrix accumulation induced by 4.25% glucose-based PDF. Tanshinone IIA also reduced TGF-ß1 and CTGF expression in parietal peritoneum as well as in omentum in a dose-dependent manner. CONCLUSION: Tanshinone IIA prevented the progression of peritoneal fibrosis in this rat model. Tanshinone IIA may be a novel therapy for peritoneal fibrosis in patients undergoing long-term PD.

Protective effects of vasonatrin peptide against hypobaric hypoxia-induced pulmonary hypertension in rats.

1. The aim of the present study was to investigate the in vivo effects of vasonatrin peptide (VNP) on hypoxia-induced pulmonary hypertension (HPH). 2. The HPH model was developed by subjecting rats to hypobaric hypoxia. The HPH rats were then treated with either VNP (50 microg/kg per day, i.p.) or saline (0.5 mL, i.p.) every day for 7 days. Haemodynamic indices, right ventricular hypertrophy (RVH) and remodelling of the pulmonary arteries were evaluated. In addition, plasma levels of atrial natriuretic peptide (ANP), endothelin (ET)-1 and angiotensin II (AngII) were determined, as was natriuretic peptide receptor-C (NPR-C) mRNA expression in the right ventricle. 3. Hypobaric hypoxia induced severe HPH compared with the normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, significantly lower levels of plasma ET-1 and AngII and cardiac NPR-C mRNA expression were observed in VNP-treated compared with saline-treated HPH rats, whereas higher plasma concentrations of ANP were found in the former group. Acute intravenous administration of 50 microg/kg VNP significantly ameliorated pulmonary haemodynamics in HPH rats. 4. Taken together, the date indicate that VNP has certain preventative and therapeutic effects against HPH.

Research on PM2.5 estimation and prediction method and changing characteristics analysis under long temporal and large spatial scale - A case study in China typical regions.

High concentration of fine particulate matter (PM2.5) has been shown to be a major contributor to haze weather, which has been associated with an increased prevalence in lung cancer. An accurate estimation and predication of PM2.5 historical levels, and its spatial-temporal variability can assist in strategically improving regional air quality and reducing its harmful effects on population health. This paper targets Beijing, Tianjin, and Hebei province (BTH), three northeast province of china (TNPC), Yangtze river delta (YRD) and pearl river delta (PRD) as the study areas. Data used in this study include PM2.5 measurements from April 2013 to December 2016, MODIS AOD raster imageries and five meteorological factors from 2000 to 2016. By combining back propagation artificial neural network (BPANN) and ε-support vector regression (ε-SVR), a novel hybrid model was constructed to impute the historical PM2.5 missing values in the long time series from 2000 to 2012, and to predict the concentration of PM2.5 from April 2014 to December 2017. The hybrid model produced results superior to BPANN and ε-SVR with a higher accuracy, lower error rate, and a stable performance. This model can be applied to the other four regions with consistent results. Results of spatial-temporal analysis indicated that the PM2.5 concentration has increased along with a pollution range expansion in BTH from 2000 to 2010. In addition, the PM2.5 concentration decreased slowly in PRD. The concentration and pollution range of PM2.5 in TNPC and YRD showed a stable trend. In 2012, the four research areas all showed decreased trend, and the pollution range narrowed. From 2013 to 2016, the PM2.5 concentration increased shortly then decreased; in particular, the high pollution areas saw a decrease in PM2.5 concentration, which correlated with control measures adopted by the state during the same time period. The hot spots of PM2.5 were mainly distributed in the inland cities.

Imaging Features of the Whole Uterus Volume CT Perfusion and Influence Factors of Blood Supply: A Primary Study in Patients with Cervical Squamous Carcinoma.

RATIONALE AND OBJECTIVES: To explore the imaging features of whole uterus volume CT perfusion (vCTP) and the influence factors of blood supply in cervical squamous carcinoma (CSC). MATERIALS AND METHODS: vCTP was performed on a 640-slice computed tomography system in 43 patients with CSC diagnosed by biopsy, and 24 cases of them underwent magnetic resonance imaging. The size of the tumor was measured on vCTP and magnetic resonance (MR) images. Perfusion parameters, including arterial blood flow (AF), blood volume, and permeability surface (PS), were measured by two radiologists, using interclass correlation coefficient to evaluate the interobserver reliability. The difference of tumor size and perfusion data was analyzed by paired t test and rank sum test. The correlation of perfusion parameters with some factors was analyzed by Pearson or Spearman correlation analysis. RESULTS: Tumor sizes were not significantly different between vCTP and MR images. The interclass correlation coefficient of each parameter was 0.818-0.945. The AF value of CSC was significantly higher than normal uterine body, and the blood volume and PS values of CSC were not statistically different compared with those of normal uterine body. There was no significant difference in AF value of CSC among different FIGO stages and pathological grades. The AF and PS values of CSC were negatively correlated with the age of the patients. CONCLUSION: The vCTP could accurately shows the size of the CSC with use of MR as the reference standard, and its perfusion parameters have good measurement stability; the CSC was hypervascular, but this trend was less pronounced in older women.

S-Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross-Tolerance In Vivo.

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of nitric oxide by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross-tolerance in Apoe-/- mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross-tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross-tolerance through PGIS S-nitrosylation at cysteine 231/441.

Anti-arrhythmic effects of kappa-opioid receptor and its changes in ischemia and reperfusion.

BACKGROUND: It remains unclear whether the kappa-opioid receptor (kappa-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the kappa-OR. Additionally, the anti-arrhythmic effect induced by kappa-OR stimulation was also determined during ischemia and reperfusion (I/R). METHODS: Rats were randomly divided into different groups according to two experimental protocols. The anti-arrhythmic effects of U50,488H, a selective kappa-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of kappa-OR mRNA and protein were measured by RT-PCR and Western blotting techniques in an I/R model of 30-min ischemia followed by 360 min of reperfusion. RESULTS: Limited numbers of premature ventricular contractions (PVCs) were revealed in the control group. Administration of U50,488H in the control group had no effect on occurrence of PVCs. Incidence of arrhythmia in the I/R group was significantly increased. Treated with U50,488H in the I/R group, the incidence of arrhythmia was significantly reduced. With prior use of nor-BNI, a selective kappa-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of kappa-OR mRNA and the density of kappa-OR protein increased significantly at 0 min, 60 min, and 180 min during reperfusion. CONCLUSIONS: The present study provides evidence for the first time that the expressions of kappa-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon kappa-OR stimulation during I/R.

Angiogenic effects of the extracts from Chinese herbs: Angelica and Chuanxiong.

Angelica and ChuanXiong are used to cure ischemic heart disease in China. Previous studies found that these two herbs could increase myocardial blood flow, oxygen-supply and keep myocardial oxygen balance, etc. However, the mechanisms of angiogenic effects of these two herbs are not well-known. The purpose of this study was to assess the effects of Angelica and ChuanXiong on vascular endothelial growth factor (VEGF) expression in rat myocardial infarction, on endothelial cell proliferation and quantity of vessels on chick embryo chorioallantoic membrane (CAM). In this study, rats were divided randomly into either pre-treatment or acute-treatment group and sacrificed at the end of the treatments. VEGF expression using Western blot analysis was significantly increased in the groups pre-treated with ChuanXiong and Angelica when compared to the control group (p < 0.05). There was significant increase in VEGF expression in the rats treated acutely with Angelica (p < 0.05). In the contrary, the rats treated with ChuanXiong showed a decrease in VEGF expression when compared to the acute-treatment control group (p < 0.05). Similar results were observed in immunohistochemistry of VEGF expression in the myocardia. Our study also demonstrated that these two herbs significantly enhanced endothelial cell proliferation (p < 0.05) and revascularity in CAM (p < 0.05). The data showed that Angelica and ChuanXiong could affect VEGF expression in rat myocardial infarction, promote endothelial cell proliferation and stimulate quantity of vessels on CAM model. The results suggest that Angelica and ChuanXiong have angiogenic effects, and may provide some mechanisms for the treatment of myocardial infarction and peripheral ischemia.

Long non-coding RNA deep sequencing reveals the role of macrophage in liver disorders.

Liver disorders such as hepatitis, cirrhosis and hepatocellular carcinoma are a series of the most life threatening diseases along with extensive inflammatory cellular infiltrations. Macrophage has been proved to be key regulators and initiators of inflammation, and long non-coding RNAs (lncRNAs) are recommended to play critical roles in the occurrence and development of a variety of diseases. To uncover the role of macrophage in liver disorders via lncRNA sequencing method, we first applied a lncRNA classification pipeline to identify 1247 lncRNAs represented on the Affymetrix Mouse Genome 430/430A 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published gene expression profiles of silica particle exposed macrophages and liver respectively, and identified and validated sets of differentially expressed lncRNAs shared by macrophages and liver. The functional enrichment analysis of these lncRNAs was processed on the basis of their expression signatures, three aspects including cis, trans and co-acting proteins were proposed. This is the first time to correlate macrophage with liver disorders via co-expressed lncRNAs. Our findings indicated that roles of macrophage in liver disorders were double-edged, the differentially expressed lncRNAs and their corresponding regulatory genes or proteins may serve as potential diagnostic biomarkers and therapeutic targets.

[The study on angiogenesis activity of danggui, chuanxiong and danshen].

OBJECTIVE: To observe the effect of danggui (Radix angelicae sinensis), chuanxiong (Rhizoma chuanxiong) and danshen (Radix salvae miltionrrhizae) on cardiac microvascular endothelial cells (CMECs) obtained from rat and quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model. METHODS: Normal rat cardiac microvascular endothelial cells (CMECs) were cultured by collagenase and trypsin and the influences of the herbs on the CMECs were observed by cell count and MTT colorimetry. The activity of blood vessels was determined by quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model. RESULTS: Compared with the normal group, after treatment with chuanxiong of high dosage, danggui of high and middle dosages, danshen of high and middle and low dosages, they enhanced proliferation significantly (P < 0.05). The two later could be in dependent dose. And the herbs might increase quantitation of vessels on CAM. CONCLUSION: These Chinese herbs may promote angiogenesis by stimulating proliferation of CMEC and incresasing blood vessels.

Inhibition of hypoxia-induced proliferation and collagen synthesis by vasonatrin peptide in cultured rat pulmonary artery smooth muscle cells.

The aim of the present research is to investigate the effects of vasonatrin peptide (VNP) on hypoxia-induced proliferation and collagen synthesis in pulmonary artery smooth muscle cells (PASMCs). Smooth muscle cells isolated from rat pulmonary artery were cultured and used at passages 3-5. Cell proliferation and collagen synthesis were evaluated by cell counts, [(3)H] thymidine and [(3)H] proline incorporation. The results showed that cells exposed to hypoxia for 24 h exhibited a significant increase in [(3)H] thymidine (93%) and [(3)H] proline (52%) incorporation followed by a significant increase in cell number (47%) at 48 h in comparison with the respective normoxic controls. VNP reduced hypoxia-stimulated increase in cell proliferation in a concentration-dependent manner from 10(-8) to 10(-6) mol/L and attenuated hypoxia-induced collagen synthesis ranging from 10(-6) to 10(-5) mol/L, which is similar to but more potent than both ANP and CNP. The action of VNP on PASMCs was mimicked by 8-bromo-cGMP (10(-4) mol/L, the membrane-permeable cGMP analog), and blocked by HS-142-1 (2 x 10(-5) mol/L), the particulate guanylyl cyclase-coupled natriuretic peptide receptor antagonist, or KT-5823 (10(-6) mol/L), the cGMP-dependent protein kinase (PKG) inhibitor. The results suggest that VNP inhibits hypoxia-stimulated proliferation and collagen synthesis in cultured rat PASMCs via particulate guanylyl cyclase-coupled receptors through cGMP/PKG dependent mechanisms.

[Inhibition of moderate hypoxia-induced protein synthesis by vasonatrin peptide in cultured neonatal rat cardiomyocytes].

The present work was to investigate the effects of vasonatrin peptide (VNP) on cardiomyocyte protein synthesis induced by moderate hypoxia. In cultured neonatal rat cardiomyocytes, MTT methods, total protein measurement and (3)H-leucine incorporation were used to calculate the cell number and measure the protein synthesis of cardiomyocytes. Furthermore, radioimmunoassay was undertaken to observe the effects of VNP on the intracellular levels of cAMP, cGMP and the concentration of endothelin (ET) in the culture medium. The results showed that both the cell number and protein synthesis decreased with severe hypoxia for 24 h. In contrast, under moderate hypoxia, cardiomyocyte hypertrophy developed; the protein synthesis as evidenced by total protein content and 3H-eucine incorporation increased significantly. VNP reduced cardiomyocyte protein synthesis induced by moderate hypoxia in a dose-dependent manner. Furthermore, VNP increased the intracellular level of cGMP and decreased the concentration of ET in the culture medium under moderate hypoxia, but had no effect on the level of cAMP. These results suggest that VNP inhibits moderate hypoxia-induced protein synthesis in cultured neonatal rat cardiac myocytes. This effect is mediated, at least in part, by an increase in intracellular cGMP, a reduction in synthesis, and/or a release in ET of cardiomyocytes.

[Vasonatrin peptide attenuates the enhancement of electrically-induced intracellular calcium transient by isoproterenol in rat cardiac myocytes].

The purpose of this study was to investigate the effects of vasonatrin peptide (VNP) on electrically-induced intracellular calcium ([Ca(2+)](i)) transient and mechanism of the effects in the cardiac myocytes. The [Ca(2+)](i) transient was measured with a fluoremetric method. The effects of HS-142-1, 8-Br-cGMP and methylene blue (MB) on [Ca(2+)](i) transient in cardiac myocytes were also determined. Isoproterenol (Iso) at 10(-10)~10(-6) mol/L augmented electrically-induced [Ca(2+)](i) transient dose-dependently, which was (13+/-8)% (P>0.05), (26+/-13)% (P< 0.05), (66+/-10)% (P<0.01), (150+/-10)% (P<0.01) and (300+/-25)% (P<0.01), respectively. These effects were blocked by an beta-adrenergic bloker propranolol (10(-6) mol/L). The effect of Iso (10(-8) mol/L) on [Ca(2+)](i) transient was attenuated in a dose-dependent manner by VNP at 10(-10)~10(-6) mol/L, which was (99+/-3)% (P>0.05), (96+/-2)% (P<0.05), (84+/-6)% (P<0.01), (66+/-3)% (P<0.01) and (62+/-3)% (P<0.01), respectively. 8-Br-cGMP (10(-7)~10(-3) mol/L) aslo attenuated 10(-8) mol/L Iso-induced [Ca(2+)](i) transient dose-dependent. The effect of VNP on [Ca(2+)](i) transient was almost abolished in the presence of HS-142-1 (2x10(-5) mol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptors. MB (10(-5) mol/L), an inhibitor of GC, not only blocked the effect of VNP in myocytes, but also augmented electrically-induced [Ca(2+)](i) transient. VNP and HS-142-1 themselves did not change the [Ca(2+)](i) transient in the cardiac myocytes significantly. But MB augmented the [Ca(2+)](i) transient in the cardiac myocytes significantly. These results suggest that VNP attenuates [Ca(2+)](i) transient induced by Iso. This effect is possibly achieved by binding VNP with the natriuretic peptide GC receptors in the myocytes, leading to an increase in intracellular cGMP.

[Vasorelaxing role of vasonatrin peptide in human intramammary artery in vitro].

The purpose of this study was to investigate the vasorelaxing effect of vasonatrin peptide (VNP) on human intramammary artery (HIMA).The vasorelaxing effect of VNP on HIMA was measured by means of perfusion in vitro. The effects of HS-142-1, TEA, 8-Br-cGMP and methylene blue (MB) were also observed. It was found that VNP caused a concentration-dependent relaxation in HIMA which was independent of the endothelium. 8-Br-cGMP (0.1-1000 micromol/L) also caused a concentration-dependent relaxation in HIMA. The vasorelaxing effect of VNP disappeared in the presence of HS-142-1 (20 micromol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptor. MB (10 micromol/L), an inhibitor of GC, not only blocked completely the relaxation of HIMA, but also enhanced the vascular contraction induced by norepinephrine. TEA (1 mmol/L), an antagonist of calcium activated potassium channels (K(Ca)), reduced but not completely blocked the vasorelaxing effect of VNP. These findings suggest that VNP can relax HIMA, which is independent of the endothelium. This effect is possibly achieved by the binding of VNP with the natriuretic peptide GC receptors in the smooth muscle cells (SMCs), leading to an increase in intracellular cGMP level. Moreover, the vasorelaxing effect of VNP is associated with K(Ca).