Cardiovascular Diseases ; Humans ; Natriuretic Peptide, C-Type

AIMTo investigate the effect of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in hypoxic rat hearts.

METHODSRats were divided randomly into three groups: control group, hypoxia group(3-28 d) and VNP (25-75 microg/kg per day) + hypoxia group. The plasma concentration of atrial natriuretic peptide (ANP) in rats was measured by the means of radioimmunoassay. Furthermore, quantitative PCR was used to examine the NPR-C mRNA level in rat hearts.

RESULTSThe plasma concentration ANP in rats was significantly higher than that of control group, and VNP (75 microg/kg per day) made it more higher. Hypoxia for 3 day of had no significant effect on the NPR-C mRNA level in rat hearts, while hypoxia for 7-28 d significantly increased the level of NPR-C mRNA in a time dependent manner. VNP (50-75 microg/kg per day) significantly reduced the NPR-C mRNA level in rat hearts in a dose dependent manner.

CONCLUSIONVNP increases the plasma concentration of ANP in hypoxic rats. Hypoxia can increase expression of NPR-C in rat hearts significantly, which can be inhibited by VNP.

Animals ; Atrial Natriuretic Factor ; blood ; pharmacology ; Hypoxia ; metabolism ; Male ; Natriuretic Peptide, C-Type ; metabolism ; Natriuretic Peptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism

Mammalian oocytes within Graafian follicles are arrested at prophase I of meiosis. C-type natriuretic peptide (NPPC), secreted by mural granulosa cells (MGCs), maintains oocyte meiotic arrest via binding to its cognate receptor natriuretic peptide receptor 2 (NPR2) and producing cyclic guanosine monophosphate (cGMP). NPR2 is most concentrated in the cumulus cells. In addition, cAMP, gap junction, inosine monophosphate dehydrogenase (IMPDH) and other important regulatory factors are also involved in meiotic arrest. Luteinizing hormone (LH) then rapidly decreases cGMP and induces oocyte meiotic resumption. In this paper, advances in the molecular mechanisms of meiotic arrest and LH-induced meiotic resumption were reviewed. This paper may provide new ideas for the prevention, diagnosis and treatment of related reproductive diseases.
Animals ; Cumulus Cells ; Female ; Luteinizing Hormone ; Meiosis ; Natriuretic Peptide, C-Type ; genetics ; Oocytes

The natriuretic peptides are a family of three peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). CNP is produced in the growth plate and acts in a paracrine/autocrine manner and has been found to play an essential role in enchondral bone growth , as demonstrated in rodents and human. Biosynthetic processing of CNP releases a bioinactive amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) and is produced in equimolar amounts with CNP. The level of NTproCNP in plasma reflects the rate of CNP biosynthesis and measured easily using commercial kit by enzyme-linked immunosorbent assay (ELISA) method. Knockout mice for CNP or its cognate receptor (NPR-B) are dwarfed. In human, homozygous loss of functional mutations in the NPR-B gene causes acromesomelic dysplasia, Maroteaux type (OMIM #602875). To clarify the role of CNP/NTproCNP in linear growth in human, some researchers measured plasma NTproCNP levels in healthy children and children with short stature due to various causes. CNP showed the heighest levels after 12 hr of life and with a progressive decline afterwards. It is proved that there is modest but significant correlation between NTproCNP level and IGF-I in healthy children and the timing of peaks in NTproCNP and IGF-I were identical in both sex. This paper will introduce recent advances of researches concerning about the role of CNP/NTproCNP in human growth in children with various conditions and suggest the future direction of this promising study field.
Animals ; Atrial Natriuretic Factor ; Bone Development ; Bone Diseases, Developmental ; Child ; Enzyme-Linked Immunosorbent Assay ; Growth Plate ; Humans ; Insulin-Like Growth Factor I ; Mice ; Mice, Knockout ; Natriuretic Peptide, Brain ; Natriuretic Peptide, C-Type ; Natriuretic Peptides ; Plasma ; Rodentia

Natriuretic peptides comprise a family of three structurally related peptides; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The present study was performed to investigate the effect of ANP on the proliferation and activity of ROS17/2.8 and HOS cells which are well-characterized osteoblastic cell lines. ANP dose-dependently decreased the number of ROS17/2.8 and HOS cells after 48-hour treatment. ANP generally increased the alkaline phosphatase activity of ROS17/2.8 and HOS cells after 48 hr treatment, regardless of the fact that basal activity of alkaline phosphatase was much lower in HOS cells compared to that of ROS17/1.8 cells. ANP increased the NBT reduction by ROS17/2.8 and HOS cells. ANP showed the variable but no significant effect on the nitric oxide production by ROS17/2.8 and HOS cells. ROS17/2.8 and HOS cells produced and secreted gelatinase into culture medium, and this enzyme was thought to be the gelatinase A type with the molecular weight determination. The gelatinase activity produced by ROS17/2.8 cells was increased by the treatment of ANP. However, the enzyme activity was not affected by ANP treatment in the HOS cell culture. In summary, ANP decreased the proliferation and increased the alkaline phosphatase activity and NBT reduction of osteoblasts. These results indicate that ANP is one of the important regulators of bone metabolism.
Alkaline Phosphatase ; Atrial Natriuretic Factor ; Cell Culture Techniques ; Cell Line ; Gelatinases ; Humans ; Matrix Metalloproteinase 2 ; Metabolism ; Molecular Weight ; Natriuretic Peptide, Brain ; Natriuretic Peptide, C-Type ; Natriuretic Peptides ; Nitric Oxide ; Osteoblasts* ; Peptides

Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-1, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, 2.84+/-1.71%, n=12, vs -0.71+/-0.86%, n=21; p<0.05) and decreased ANP release (-9.02+/-3.36%, n=14, vs 1.35+/-3.25%, n=23; p<0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.
Atrial Natriuretic Factor ; Blood Pressure ; Cyclic Nucleotide Phosphodiesterases, Type 5* ; Extracellular Fluid ; Guanylate Cyclase ; Humans ; Natriuretic Peptide, C-Type ; Stroke Volume ; Tissue Donors ; Sildenafil Citrate

OBJECTIVETo investigate the influence of human C-type natriuretic peptide (hCNP) on proliferation of vascular endothelial cells (HUVECs).

METHODSReconstructed pcDNA3.1 (+)/hCNP was transfected into HUVECs with polyethylenimine and its plasmid expression was examined with RT-PCR, immunohistochemistry and Western blot. MTT method was used to determine the effect of expressed protein on proliferation of HUVECs. pcDNA3.1 (+)/hCNP transfection was used for control.

RESULTSThe proliferation of HUVEC 48 h after pcDNA3.1 (+)/hCNP transfection was (0.301 +/- 0.096), which was obviously higher than that with pcDNA3.1 (+) transfection (0.164 +/- 0.012). Reconstructed pcDNA3.1 (+)/hCNP might be expressed in HUVECs effectively and its protein expression was capable of promoting HUVECs proliferation markedly.

CONCLUSIONThe successive expression of reconstructed pcDNA3.1 (+)/hCNP and the promoting activity of its expressed protein on HUVECs lay the foundation potential therapeutic value of C-type natriuretic peptide.

Cell Line ; Cell Proliferation ; Endothelial Cells ; cytology ; Humans ; Natriuretic Peptide, C-Type ; genetics ; Plasmids ; RNA, Messenger ; genetics ; Transfection

Animals ; Brain Injuries ; blood ; cerebrospinal fluid ; chemically induced ; Endotoxins ; toxicity ; Female ; Male ; Natriuretic Peptide, C-Type ; analysis ; Neurotensin ; analysis ; Rabbits

OBJECTIVETo observe the correlation of plasma amino-terminal pro-A-, B- and C-type natriuretic peptide (NT-proANP, NT-proBNP and NT-proCNP) levels with New York Heart Association (NYHA) functional class and echocardiographic derived parameters of cardiac function in heart failure patients.

METHODSData of NYHA grade, echocardiographic derived parameters of cardiac function, plasma levels of NT-proANP, NT-proBNP and NT-proCNP (measured by enzyme immunoassay method) were obtained in 112 heart failure patients and 44 normal control subjects. The correlation analysis was made between NT-proANP, NT-proBNP, NT-proCNP and NYHA functional class, left atrium diameter (LAD), left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF), respectively.

RESULTSThe plasma concentrations of NT-proANP, NT-proBNP and NT-proCNP in heart failure patients were significantly higher than in control group (all P<0.05). Correlation analysis revealed a strong correlation between NT-proANP and NT-proBNP (r = 0.790, P = 0.000) and a weak correlation between NT-proCNP and NT-proBNP (r = 0.278, P = 0.003) as well as between NT-proCNP and NT-proANP (r = 0.236, P = 0.012) in heart failure patients. Univariant analysis showed that NT-proANP and NT-proBNP were positively correlated to LAD, LVEDD and negatively correlated to LVEF (all P<0.05) while there was no significant correlation between NT-proCNP and echocardiographic derived parameters of cardiac function in heart failure patients. Multivariate stepwise regression analysis including age, gender, NYHA classification, LAD, LVEDD and LVEF revealed that NYHA classification, LVEF, LAD and age were independent predictors of NT-proANP; while NYHA classification, LVEF and age were independent predictors of NT-proBNP while there was no association among these factors and NT-proCNP.

CONCLUSIONIn heart failure patients, the plasma concentration of NT-proANP, NT-proBNP and NT-proCNP were significantly increased and NT-proANP, NT-proBNP but not NT-proCNP were significantly correlated to NYHA classification and echocardiographic derived parameters of cardiac function.

Adult ; Aged ; Atrial Natriuretic Factor ; blood ; Case-Control Studies ; Echocardiography ; Female ; Heart Failure ; blood ; diagnostic imaging ; physiopathology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Natriuretic Peptide, C-Type ; blood ; Ventricular Function, Left

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51+/-11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268+/-1.800 pg/mL vs. 3.342+/-1.150 pg/mL, p=0.002; CK-MB, 2.54+/-1.03 ng/dL vs. 1.86+/-0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76+/-4.99 mg/L vs. 3.13+/-4.88 mg/L, p=0.789; NT pro-BNP, 49+/-47 pg/mL vs. 57+/-63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.
Acetylcholine ; Angina Pectoris, Variant ; Atherosclerosis ; Biomarkers ; C-Reactive Protein ; Coronary Angiography ; Coronary Vessels ; Creatine Kinase ; Endothelium ; Humans ; Immunoassay ; Myoglobin ; Natriuretic Peptide, C-Type ; Plasma ; Sensitivity and Specificity ; Spasm