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

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

There are many established and proposed bio-molecular markers for cardiovascular disease, including vasoactive substances, substances related to inflammation and oxidative stress, and substances involved in tissue structure and remodeling. Among these substances, we focused on natriuretic peptides and adrenomedullin (AM) as clinically useful bio-molecular markers in this review. Three natriuretic peptides-atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)-play various important roles in the cardiovascular system. ANP and BNP are released from the heart and exist primarily as circulating hormones. They participate in the regulation of blood pressure and fluid levels. Plasma levels of ANP and BNP are increased in various pathological conditions such as heart failure, myocardial infarction, and hypertension with cardiac hypertrophy. BNP is now essential as a biochemical marker in managing patients with cardiovascular disease. CNP is mainly produced in vascular endothelium. It contributes to smooth muscle relaxation and growth inhibition as a local hormone, but it is also synthesized in cardiac fibroblasts and inhibits fibroblast proliferation and myocyte growth. However, the significance of plasma CNP levels remains to be elucidated. AM is widely distributed in various organs and tissues, including the cardiovascular system. Not only it is a potent vasodilator peptide, but it also has protective effects against vascular and cardiac cell injury and excessive growth. Plasma AM levels are increased in several cardiovascular diseases, including hypertension, heart failure, myocardial infarction, and atherosclerotic disease, and AM appears to be a predictive and prognostic marker in the setting of cardiovascular disease.
Adrenomedullin ; Atherosclerosis ; Atrial Natriuretic Factor ; Biomarkers ; Blood Pressure ; Cardiomegaly ; Cardiovascular Diseases ; Cardiovascular System ; Endothelium, Vascular ; Fibroblasts ; Heart ; Heart Failure ; Humans ; Hypertension ; Inflammation ; Muscle Cells ; Muscle, Smooth ; Myocardial Infarction ; Natriuretic Peptide, Brain ; Natriuretic Peptide, C-Type ; Natriuretic Peptides ; Oxidative Stress ; Plasma ; Relaxation

BACKGROUND: Recently, B-natriuretic peptide (BNP) level and left atrial volume index (LAVi) were known to correlate with indices of LV diastolic function. As a screening method, we tried to evaluate the efficacy to BNP, ANP, and LAVi to predict the advanced diastolic dysfunction that means myocardial relaxation abnormality and elevated LV filling pressure. METHODS: In 100 patients who referred for echocardiography, Doppler recording of the mitral inflow and tissue Doppler imaging of the mitral annulus were obtained and classified into 4 diastolic function grades (normal, impaired relaxation, pseudonormal, and restrictive). Advanced diastolic dysfunction was defined as pseudonormal and restrictive physiology. LAVi was measured by modified Simpson's method in apical 4-chamber view at end-systole. Plasma levels of BNP and ANP were measured on the same day as echocardiogram was done. RESULTS: BNP and ANP levels were increased as diastolic function grade was worsening (BNP : 60+/-92, 108+/-204, 778+/-1,023 and 1,426+/-1,421 pg/ml, p<0.001; ANP: 22+/-30, 23+/-26, 94+/-92, 96+/-61 pg/ml, p<0.001). LAVi was also increased as diastolic dysfunction was advanced: 24+/-7 ml/m2, 27+/-9 ml/m2, 37+/-12 ml/m2, 45+/-12 ml/m2, p<0.001. The areas under the curve of receiver-operator characteristic curve for BNP, ANP and LAVi to detect the advanced diastolic dysfunction were 0.91, 0.88 and 0.84, respectively. BNP of 137 pg/ml, ANP of 34 pg/ml, and LAVi of 30 ml/m2 were the best values of sensitivity and specificity, respectively. CONCLUSION: These data suggest that BNP, ANP and LAVi provide meaningful sensitivity and specificity for the detection of advanced diastolic dysfunction, respectively. Among these, BNP is better than ANP or LAVi for the screening method to predict the advanced diastolic dysfunction.
Atrial Natriuretic Factor ; Diastole ; Echocardiography, Doppler ; Heart Atria ; Humans ; Mass Screening* ; Natriuretic Peptide, Brain ; Natriuretic Peptides* ; Physiology ; Plasma ; Relaxation ; Sensitivity and Specificity

We examined the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs upon isoproterenol (Iso)-induced cardiac hypertrophy in rats. Then, we tried to investigate the effects of sympatholytics to see if they can modulate the expression of ANP and BNP. In this study, RT-PCR technique was used to characterize the expression of ANP and BNP in right atrium (RA) and left ventricle (LV) of the hypertrophied rat heart. Histologic findings indicated that stimulation of beta-adrenoceptors with Iso for 5 days was sufficient to induce cardiac hypertrophy in rats. A continuous stimulation with Iso for 7 days resulted in an increase of the ANP and BNP expression in the LV and BNP expression in the RA. The increased expressions of ANP and BNP in the LV were slightly inhibited, and the increased expressions of BNP in the RA were markedly inhibited by a continuous treatment with propranolol, metoprolol, and clonidine for 7 days. Overall, our data present a differential expression of the natriuretic peptides in Iso-induced cardiac hypertrophy, and that the mechanisms involved in this differential ANP and BNP gene expression could be mediated via sympathetic nervous system.
Animals ; Atrial Natriuretic Factor ; Cardiomegaly* ; Clonidine ; Gene Expression ; Heart ; Heart Atria ; Heart Ventricles ; Isoproterenol ; Metoprolol ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Propranolol ; Rats* ; RNA, Messenger* ; Sympathetic Nervous System ; Sympatholytics

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

BACKGROUND: Head-down suspension (HDS) of rats has been used as a model for the simulation of a microgravity environment. Natriuretic peptide family including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptides (CNP), and their receptors are responsible for body fluid homeostasis and blood pressure control. However, little is known about the long-term responses and the simultaneous observations of both natriuretic peptide family and their receptors following HDS. This study was analyzed the regulation of cardiac, hypothalamic and renal natriuretic peptides and their receptors syntheses to 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45degrees head-down tilt using the tail-traction technique (HDS rats). This study observed the cardiac, hypothalamic and renal syntheses of natriuretic peptides as a expression of ANP, BNP and CNP mRNA. The mRNA expressions of A-type natriuretic peptide receptor (NPR-A), B-type NPR (NPR-B) and clearance receptor (NPR-C) were also determined. The expressions of natriuretic peptide and their receptor mRNA were measured by reverse transcription-polymerase chain reaction with [32P]-dCTP following 4 weeks of HDS in both control and HDS rats. RESULTS: After 4 weeks of HDS, the expressions of ANP mRNA were significantly decreased in the right atrium and the kidney, and showed the non-significant decreasing trend in the left atrium and the hypothalamus of HDS rats. BNP mRNA expressions were decreased in the heart especially in the left atrium, while its mRNA in the left ventricle was showed the non-significant increasing trend following 4 weeks of HDS. The expressions of CNP mRNA were increased in the hypothalamus and showed the non-significant increasing trend in the kidney of the HDS rats. After 4 weeks of HDS, NPR-A mRNA expressions were decreased in the kidney and hypothalamus, but NPR-C mRNA expression was showed the non-significant increasing trend in the kidney of HDS rats compared with controls. CONCLUSION: These results suggest that the regulation of natriuretic peptide mRNA following 4 weeks of HDS exerts to maintain the blood volume through an attenuation of syntheses in natriuretic peptide family of the heart and the kidney.
Animals ; Atrial Natriuretic Factor ; Blood Pressure ; Blood Volume ; Body Fluids ; Head-Down Tilt ; Heart ; Heart Atria ; Heart Ventricles ; Homeostasis ; Humans ; Hypothalamus ; Kidney ; Male ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Rats* ; Rats, Sprague-Dawley ; Receptors, Peptide ; RNA, Messenger* ; Weightlessness

BACKGROUND: Head-down suspension (HDS) of rats has evolved as a useful model for the simulation of a microgravity environment. Atrial natriuretic peptides (ANP) and brain natriuretic peptide (BNP) have been considered to comprise the cardiac natriuretic peptide family responsible for body fluid homeostasis and blood pressure control. However, little is known about the long-term responses and the simultaneous observations of both ANP and BNP following HDS. Therefore, this study was aimed to characterize the long-term adaptations of cardiac ANP and BNP syntheses to 4 weeks of HDS in rats. METHOD: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a 45degree head-down tilt using the tail-traction technique (HDS rats). We determined the cardiac synthesis of natriuretic peptides as a expression of ANP and BNP mRNA, The expressions of natriuretic peptide mRNA were measured by reverse transcription-polymerase chain reaction with [32P]-dCTP following 4 weeks of HDS in the each cardiac chamber of control and HDS rats. RESULT: After 4 weeks of HDS, the expressions of ANP mRNA were decreased in the both right (p<0.05) and left atria. The ANP mRNA in the ventricles did not show significant changes compared with control values. In contrast with ANP, BNP mRNA was only decreased in the left atrium (p<0.05) and revealed the non-significant decreasing trend in the right ventricle. There were no remarkable changes of BNP mRNA expression compared with control rats in the both right atrium and left ventricle. CONCLUSION: Collectively, these results represent that the cardiac syntheses of natriuretic peptides following 4 weeks of HDS are attenuated to prevent any decrement of body fluid as a long-term adaptive response to simulated microgravity and ANP and BNP genes have the differential expression in the each chamber of the heart.
Animals ; Atrial Natriuretic Factor ; Blood Pressure ; Body Fluids ; Head-Down Tilt ; Heart ; Heart Atria ; Heart Ventricles ; Homeostasis ; Humans ; Male ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger* ; Weightlessness

BACKGROUND: C-type natriuretic peptide (CNP), secreted from endothelial cells, dilates the vessel and increases the renal excretion of sodium and water. Plasma CNP level is not elevated in patients with congestive heart failure (CHF), but the myocardial content of CNP is increased, suggesting paracrine or autocrine role of CNP. We studied to compare the effect of ANP and CNP on vasorelaxation in CHF rat model. METHODS: Coronary artery ligation was performed in Sprague Dawley rats, resulting in CHF (n=5) and they were fed with ordinary chow for 10 weeks. After measuring hemodynamics, aorta and pulmonary artery were incised and studied in organ chamber to measure the isotonic force to KCl and to observe the relaxation response to atrial natriuretic peptide (ANP), and CNP in vessels precontracted with phenylephrine. Normal Sprague Dawley rats (n=5) were used as control. RESULTS: There were no difference in vasorelaxation responses to ANP between control and CHF rats. The response to CNP was significantly impaired in both aorta and pulmonary artery of CHF rats compared to control rats.
Animals ; Aorta* ; Atrial Natriuretic Factor ; Coronary Vessels ; Endothelial Cells ; Estrogens, Conjugated (USP)* ; Heart Failure* ; Hemodynamics ; Humans ; Ligation ; Models, Animal ; Myocardial Infarction ; Natriuretic Peptide, C-Type* ; Natriuretic Peptides ; Phenylephrine ; Plasma ; Pulmonary Artery* ; Rats* ; Rats, Sprague-Dawley ; Relaxation* ; Sodium ; Vasodilation

The measurements of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP), when taken together with conventional clinical assessment, may assist in making the prognosis and also for making serial adjustment of such treatment. But although such commercial assays are currently approved for the diagnosis of heart failure, the role of the natriuretic peptides for monitoring the success of congestive heart failure (CHF) therapy has not as yet been submitted for regulatory approval. Moreover, because of the intra-individual biologic variation of the BNP or because of multiple factors that affect the BNP levels, the magnitude of the change of BNP levels must be large to confidently interpret BNP changes within an individual, and just how large has not been determined. Yet the levels of plasma BNP and NT-pro BNP are well correlated with the concurrent haemodynamic measurements and indicators of left ventricular systolic function. Also, BNP and NT-pro BNP serve as significant prognostic information and it is possible that adjustment of anti-heart failure therapy according to serial measurements of BNP (in addition to the standard clinical assessment) may offer improved outcomes. Better understanding of the test characteristics is needed before we can effectively use this valuable test to guide therapeutic strategies.
Diagnosis ; Heart Failure* ; Heart* ; Humans ; Natriuretic Peptide, Brain* ; Natriuretic Peptides ; Plasma ; Prognosis