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

Anxiety disorder is one of the most common mental disorders and seriously impairs the physical and mental health of patients. Due to the efficacy of acupuncture for tranquilization, acupuncture displays its unique advantage on the treatment of anxiety disorder, but the relevant biological mechanism has not been elaborated. The modern medicine study has proved that the heart and brain have their own independent natriuretic peptide (NP) system. The dysfunction of ANP and its receptor are closely related to the occurrence of anxiety disorder. The ANP acts on anti-anxiety. Hence, focusing on the three aspects, named the anti-anxiety effect of acupuncture based on its tranquilizing effect, the anti-anxiety effect of ANP and the positive regulation of acupuncture on NP, the mechanism on ANP and its receptor was explored in anti-anxiety with acupuncture based on tranquilizing effect, and the idea was put forward on that the anti-anxiety effect of acupuncture was possibly based on its action of tranquilization through regulating the ANP and its receptor. As a result, it is expected to provide the theoretic support for the mechanism study on anti-anxiety with acupuncture based on its tranquilizing effect.
Acupuncture Therapy ; Animals ; Anti-Anxiety Agents ; metabolism ; Anxiety ; metabolism ; therapy ; Atrial Natriuretic Factor ; metabolism ; Humans ; Receptors, Atrial Natriuretic Factor ; metabolism

OBJECTIVETo explore possible mechanism of electroacupuncture (EA) for regulating immune function in anxiety disorder (AD) rats by observing the effect of acupuncture on the histology of thymus and expressions of atrial natriuretic peptide (ANP) and natriuretic peptide receptor type A (NPR- A) in thymus.

METHODSTotally 34 SD healthy rats were randomly divided into the blank control group (n = 10), the model group (n = 12), the EA group (n = 12). Anxiety model was established in rats of the model group and the EA group by using chronic unpredictable stress (CUS) stimulation. EA (15/25 Hz) at Neiguan (PC6) and Shenmen (HT7) was performed in the EA group, with 15-min needle retaining, once every other day, 15 days in total. Needle was fixed at same acupoints for 15 min without electric stimulus in the other two groups. Anxiety-like behavior was measured by elevated plus-maze (EPM) test. Pathological changes of thymus tissue were observed by optical microscope. Expressions of ANP and NPR-A in thymus were measured by immunohistochemical assay.

RESULTSThe thymus tissue in the model group was severely atrophied, with unclear structure of thymic lobules, unclear margin of thymic medulla, loosely arranged lymphocytes ,and obviously enlarged volume of thymic corpuscle. The thymus tissue in the EA group was mildly atrophied, with existent structure of thymic lobules, clear margin of thymic medulla, densely arranged lymphocytes in cortical region, and widened medullary area. Com- pared with the blank control group, the percentage of open-arms entries (OE%) in the total QE times ob- viously decreased in the model group (P < 0.05), ANP expression obviously increased (P < 0.05), and NPR-A expression obviously decreased (P < 0.01). Compared with the model group, OE% was obviously elevated (P < 0.05), ANP expression obviously decreased (P < 0.05), and NPR-A expression obviously increased (P < 0.01) in the EA group.

CONCLUSIONEA not only could reduce anxiety of rats, but also could improve chronic stress induced thymus injury through intervening synthesis and secretion of ANP, as well as the expression of NPR-A (a specific receptor of ANP).

Acupuncture Points ; Animals ; Anxiety Disorders ; therapy ; Atrial Natriuretic Factor ; metabolism ; Electroacupuncture ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism ; Thymus Gland ; pathology

BACKGROUND: The present study was aimed to determine the pathophysiological implications of local atrial natriuretic peptide (ANP) system in the kidney in two- kidney, one clip (2K1C) hypertension. METHODS: Rats were made 2K1C hypertensive, and their mRNA expressions of ANP and natriuretic peptide receptors (NPR) were determined in the clipped and contralateral kidneys by reverse transcription-polymerase chain reaction. RESULTS: The expression of ANP was decreased in the clipped kidney and increased in the contralateral kidney. Similarly, the expression of both NPR-A and NPR-C was decreased in the clipped kidney and increased in the contralateral kidney. CONCLUSION: These findings indicate a differentially-altered ANP system in the clipped and the contralateral kidneys in 2K1C hypertension.
Animals ; Atrial Natriuretic Factor ; Hypertension* ; Kidney* ; Rats ; Receptors, Peptide ; RNA, Messenger

OBJECTIVETo investigate the expressions of brain natriuretic peptide (BNP) and natriuretic peptide receptor (NPR-A) in the cord dorsal horn ganglion (DRG) of rat models of chronic nonbacterial prostatitis (CNP) and the relation of BNP and NPR-A with CNP-induced chronic pain.

METHODSWe established CNP models in 30 healthy clean SD rats using Freund's complete adjuvant, and included another 10 in a sham-operation group. The prostate tissues were subjected to HE staining, and the expressions of BNP and NPR-A in the L5-S2 DRGs were detected by real-time PCR.

RESULTSHigher degree of inflammation was related to longer modeling time. At 3, 7 and 10 days, the expressions of BNP in the CNP models were 2.16 +/- 0.35, 1.61 +/- 0.21 and 1.32 +/- 0.36, and those of NPR-A were 2.75 +/- 0.06, 2.15 +/- 0.15 and 1.04 +/- 0.13, respectively, significantly higher at 3 and 7 days as compared with the sham-operation group (P<0.05), but with no statistically significant difference at 10 days.

CONCLUSIONBNP and NPR-A are expressed in the L5-S2 DRGs of SD rats and their expressions can be upregulated by CNP. BNP and NPR-A may be involved in the mechanisms of CNP-induced pain.

Animals ; Disease Models, Animal ; Ganglia, Spinal ; metabolism ; Male ; Natriuretic Peptide, Brain ; metabolism ; Prostatitis ; 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. Atrial natriuretic peptide (ANP), C-type natriuretic peptides (CNP) and their receptors are found in the kidney, suggesting that these peptides could play a significant physiological role in the kidney. Therefore, this study was investigated the changes in the adaptations of renal natriuretic peptides and their receptors syntheses after 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45degreeshead-down tilt using the tail-traction technique (HDS rats). This study observed the renal syntheses of natriuretic peptides as a expression of ANP and CNP mRNA, and also determined the expression of A-type natriuretic peptide receptor (NPR-A) mRNA and B-type NPR (NPR-B) mRNA. The expressions of natriuretic peptide and NPR mRNA were measured by reverse transcription-polymerase chain reaction with [(32)P]-dCTP following 4 weeks of HDS in the kidney of both control and HDS rats. RESULTS: After 4 weeks of HDS, the expression of ANP mRNA significantly (P<0.01) decreased, while CNP mRNA expression was showed the non-significant increasing trend in the kidney of HDS rats. NPR-A, which binds with ANP, was significantly (P<0.001) decreased in renal mRNA expression of HDS rats compared with controls. Expression in mRNA of NPR-B, which binds with CNP, showed a slightly decreasing trend in the kidney of rats following HDS. CONCLUSION: These results suggest that the renal adaptation following 4 weeks of HDS exerts to maintain the blood volume and electrolyte balance through attenuation of syntheses in the natriuretic peptide and its binding receptor, especially in ANP rather than in CNP systems.
Animals ; Atrial Natriuretic Factor ; Blood Volume ; Humans ; Kidney ; Male ; Natriuretic Peptides* ; Peptides ; Rats* ; Rats, Sprague-Dawley ; Receptors, Peptide ; RNA, Messenger* ; Water-Electrolyte Balance ; Weightlessness

OBJECTIVE: To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide (ANP), and to analyze the potential role of ANP signaling in the pathogenesis of asthma.
 METHODS: We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-γ and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of natriuretic peptide receptor A (NPRA), transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot.
 RESULTS: The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell (PBMC) from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively (P<0.05). Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency (P<0.05). In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-γ/IL-4 (r=-0.85, P<0.05; r=-0.88, P<0.05, respectively).
 CONCLUSION Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.
Asthma ; Atrial Natriuretic Factor ; Enzyme-Linked Immunosorbent Assay ; Fetal Proteins ; GATA3 Transcription Factor ; Humans ; Hypersensitivity ; Interleukin-4 ; Leukocytes, Mononuclear ; RNA, Messenger ; Receptors, Atrial Natriuretic Factor ; Signal Transduction ; T-Box Domain Proteins

PURPOSE: The expression of natriuretic peptides in the neural bundles of the anterior portion of the optic nerves and their functions in regulating vessel tone and blood flow may suggest a possible role in the pathogenesis of glaucoma. The purpose of this study was to investigate the association between normal-tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa) and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A, and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene were determined using the restriction fragment length polymorphism and the SNaPshot methods. The genotype and allele frequencies of these polymorphisms in patients with NTG and normal controls were compared using the Fisher's exact test and the chi-square test. RESULTS: In both groups, the genotype distributions were in accordance with the Hardy-Weinberg equilibrium. There was no significant difference in the frequency of the Nppa and Npr1 alleles or genotypes in the normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease.
Receptors, Atrial Natriuretic Factor/*genetics ; *Polymorphism, Single Nucleotide ; Middle Aged ; Male ; *Intraocular Pressure ; Humans ; Guanylate Cyclase/*genetics ; Glaucoma/genetics/*physiopathology ; Genotype ; Gene Frequency ; Female ; Atrial Natriuretic Factor/*genetics ; Adult

PURPOSE: Atrial natriuretic peptide(ANP) is a hormone with diuretic and natriuretic properties that is released by the atrial stretch and plays an important role in sodium and volume homeostasis. We studied plasma ANP concentration and the influence of ANP on sodium balance after birth in low birth weight neonates on the basis of 34 wks gestational age when the nephrogenesis was completed. METHODS: Twenty low birth weight neonates without congenital heart disease, respiratory insufficiency, renal disease or sepsis born between June 1997 and December 1997 at Korea University Guro Hospital were enrolled in this study. Blood sampling for ANP was done at 6 hr, 12 hr, 24 hr, 3 days, 4 days and 10 days after birth. FENa was calculated by blood and urine electrolyte and creatinine. We analyzed the correlation of plasma ANP concentration and fractional Na excretion rate(FENa). RESULTS: Plasma ANP concentration of low birth weight neonates less than 34 wks was 63.67+/-12.94pg/ml at 6 hr after birth and peaked at 24 hr(110.67+/-6.34pg/ml). Thereafter, it gradually decreased and reached 42.43+/-21.89pg/ml at 10 days(P<0.05). Plasma ANP concentration of low birth weight neonates more than 34 wks was 25.50+/-8.22pg/ml at 6 hr after birth and peaked at 12hours(152.67+/-39.93pg/ml). Thereafter, it gradually decreased and reached 42.78+/-17.67pg/ml at 10 days(P<0.001). And plasma ANP concentration did not correlate significantly with FENa in low birth weight neonates less than 34 wks(r=0.02, P=0.09), but there was good correlation between plasma ANP and FENa in low birth weight neonates more than 34 wks(r=0.6, P<0.001). CONCLUSION: From the above results, it is concluded that ANP influences renal Na excretion after 34-week gestational age when the development of distal tubule, containing ANP receptors, is rapid and contributes to body fluid and Na homeostasis.
Atrial Natriuretic Factor ; Body Fluids ; Creatinine ; Gestational Age ; Heart Defects, Congenital ; Homeostasis ; Humans ; Infant, Low Birth Weight* ; Infant, Newborn ; Infant, Newborn* ; Korea ; Parturition* ; Plasma* ; Receptors, Atrial Natriuretic Factor ; Respiratory Insufficiency ; Sepsis ; Sodium

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.
Animals ; Atrial Natriuretic Factor ; pharmacology ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Cyclic GMP ; metabolism ; Depression, Chemical ; Female ; Guanylate Cyclase ; metabolism ; Isoproterenol ; pharmacology ; Male ; Myocytes, Cardiac ; metabolism ; Rats ; Receptors, Atrial Natriuretic Factor ; metabolism