Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis of allergic asthma / 中南大学学报(医学版)

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.

Effect of Acupuncture on Histology of Thymus and Expressions of ANP and NPR-A in Anxiety Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Totally 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>EA 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).</p>

Mechanism on atrial natriuretic peptide receptor in anti-anxiety with acupuncture based on its tranquilizing effect / 中国针灸

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.

Estrogen stimulates cell proliferation and regulates the expression of proteins in C-type natriuretic peptide signaling pathway during chondrogenesis in ATDC5 cells / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of estrogen on cell proliferation and expression of proteins of C-type natriuretic peptide (CNP), natriuretic peptides B receptor (NPR-B) and natriuretic peptides C receptor (NPR-C) in ATDC5 cells during chondrogenesis.</p><p><b>METHOD</b>ATDC5 cells were induced for differentiation with insulin 10 µg/ml (day 0), and were started to be investigated on day 6. They were incubated with: (1) Estradiol (E2) at different concentrations (10(-11)-10(-5) mol/L) for 24 hours (for studying cell proliferation), or for 48 hours (for studying CNP, NPR-B and NPR-C protein expression); (2) E2 (10(-8) mol/L) for 24, 48, 72, 96 and 120 h (for studying cell proliferation), or for 24, 48, 72 and 96 hours (for studying CNP, NPR-B and NPR-C protein expression); (3) E2 (10(-8) mol/L) , and/or ICI 182782 (estrogen receptor antagonist ) (10(-7) mol/L) for 24 hours (for studying cell proliferation). ATDC5 cells proliferation were determined by MTT (OD value). Western-blotting was performed to identify the protein levels of CNP, NPR-B and NPR-C.</p><p><b>RESULT</b>(1) After incubation with E2 (10(-11)-10(-5) mol/L) for 24 h, ATD5 cell number increased with the increasing E2 concentration, peak in E2 concentrations of 10(-9) and 10(-8) mol/L (0.56 ± 0.06 and 0.52 ± 0.02, P < 0.05 and <0.01, respectively) , while significantly decreased in E2 (10(-5) mol/L) (0.30 ± 0.02) compared with DMSO-control (0.38 ± 0.02) (P < 0.05). After incubation with E2 (10(-11)-10(-5) mol/L) for 48 h, the protein level of CNP, NPR-B and NPR-C increased significantly, with the greatest effect seen at a concentration of 10(-10) mol/L E2 for CNP and NPR-B, 10(-9) mol/L E2 for NPR-C (P < 0.05). (2) After incubation with E2 (10(-8) mol/L) for 24 to 96 hours: (1) The cell number in each of the four time points was significantly increased compared with DMSO-control, with the greatest effect in 48 h (0.030 ± 0.003) (P < 0.05 or <0.01, respectively). While the cell number at 120 h was similar to that in DMSO-control. (2) The protein level of CNP increased significantly at 24 h (P < 0.05), seemed to be increased at 48 h and 72 h and decreased at 96 h. Both NPR-B and NPR-C level seemed to be increased at 24 h (P = 0.060 and 0.055, respectively) and seemed to decrease at 48 h, with decreasing significantly at both 72 h and 96 h (P < 0.05). (3) After incubation for 24 h, there was significant difference among the cell number of the four groups (P < 0.05). Cell number of group E2 (0.470 ± 0.032) was increased compared with group (E2+ICI) (0.410 ± 0.018), both being increased compared with group DMSO-control (0.370 ± 0.011, P < 0.05, respectively). There was no difference in cell number between group ICI 182782(0.360 ± 0.035) and group DMSO-control.</p><p><b>CONCLUSION</b>E2 promotes the proliferation of ATDC5 cells i.e. chondrogenesis via estrogen receptor mediated mechanism, in both concentration-dependent and time-dependent manner. E2 (10(-11)-10(-8) mol/L) up-regulates protein expression of CNP, NPR-B and NPR-C of ATDC5 cells during chondrogenesis, and regulate the expression of the three proteins mentioned above positively or negatively at different time point, which implied that estrogen is one of the regulators of CNP signaling pathway.</p>

Angiotensin-II down-regulates cardiac natriuretic peptide receptor-A mediated anti-hypertrophic signaling in experimental rat hearts.

Atrial natriuretic peptide (ANP) exerts anti-hypertrophic effects in the heart via natriuretic peptide receptor-A (NPR-A). However, ANP mediated anti-hypertrophic activity is decreased in the cardiomyopathic conditions. In the present investigation the in vivo effects of angiotensin II (Ang II), a hypertrophic agonist have been studied on the ventricular expression level of NPR-A in Wistar rat hearts. NPR-A expression at the protein and mRNA levels were found to be markedly reduced by 5-fold respectively in Ang II infused rats heart as compared with sham rat hearts. Moreover, cGMP production in response to ANP was reduced by 77% in the isolated cardiac membrane preparation from the Ang II infused rat hearts. Losartan treatment reversed NPR-A expression and responsiveness to ANP. This study suggests that Ang II down regulates cardiac NPR-A activity by suppressing Npr1 gene transcription.

Detection of guanylate cyclase C mRNA and cytokeratin 20 mRNA in peripheral blood and analysis of prognosis in early to moderate colorectal cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the associations of guanylate cyclase C (GC-C) mRNA and cytokeratin 20 (CK20) mRNA with metastasis and prognosis in early to moderate colorectal cancer patients.</p><p><b>METHODS</b>GC-C mRNA and CK 20 mRNA in peripheral blood of 74 colorectal cancer patients without distant metastasis were detected by fluorescent quantitative PCR (FQ-PCR). Based on their clinicopathological and postoperative follow-up data, the relationship and clinical significance of these data with metastasis hazards and prognosis factors were analyzed.</p><p><b>RESULTS</b>The positive rate of GC-C mRNA in 74 colorectal cancer patients was 33.8% (25/74), and CK20 mRNA was 31.1% (23/74). The 1-, 2-, 3- year disease-free survival rates of patients were 94.6%, 82.4% and 78.4% respectively. There were significant differences in positive rates of GC-C mRNA and CK20 mRNA, tumor differentiation, mesentery lymph node metastasis, tumor embolus in vessel and postoperative chemotherapy associated with 3-year disease free survival rate by Kaplan-Meier analysis (all P<0.05). While mesentery lymph node metastasis and tumor embolus in vessel were independent risk factors of 3-year disease-free survival (P<0.05). CK20 mRNA and tumor embolus in vessel were independent risk factors of 3-year disease-free survival by analysis stratified with clinical stage (P<0.05).</p><p><b>CONCLUSIONS</b>Detection of CK20 mRNA and GC-C mRNA in peripheral blood may be important for early detection of early metastasis of colorectal cancer.</p>

Regulation of C-type natriuretic peptides and natriuretic peptide receptor-B expression in diabetic rats renal treated by Tongluo Recipe / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of C-type natriuretic peptides (CNP) and natriuretic peptide receptor-B (NPR-B) receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe (TLR).</p><p><b>METHODS</b>Sixty male SD rats were divided into 3 groups: the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin (STZ)-induced diabetic rats were treated with TLR (1.0 g·kg(-1)·d(-1)) for 4 and 12 weeks, respectively. (1) The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. (2) CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction (PCR) on rats renal cortex. (3) Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay (ELISA). (4) Pathological evaluation and NPR-B immunostaining for renal tissue were also performed.</p><p><b>RESULTS</b>(1) CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. (2) Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. (3) Renal lesions like glomerular volume increased are observed mostly in the relative early stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement.</p><p><b>CONCLUSION</b>CNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.</p>

Role of C-type natriuretic peptide receptor and large-conductance calcium-activated potassium channels in brain natriuretic peptide-induced porcine coronary artery dilation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the role of C-type natriuretic peptide receptor (NPR-C) and large-conductance calcium-activated potassium channels (BK(Ca)) in brain natriuretic peptide (BNP) induced porcine coronary artery dilation.</p><p><b>METHODS</b>Porcine coronary artery rings were obtained and treated with BNP (10(-6) mol/L), BNP + NPR-C antagonist cANF4-28 (10(-6) mol/L) and BNP + BK(Ca) blocker tetraethylammonium (TEA, 1 mmol/L). The vascular tone experiments were observed on 10 vessel segments. BK(Ca) current density was measured by the whole-cell patch clamp technique.</p><p><b>RESULTS</b>The maximum diastolic rate was similar between BNP group (68.51% ± 11.50%) and cANF4-28 + BNP group (65.67% ± 11.90%, P > 0.05) while significantly reduced in TEA + BNP group (28.87% ± 4.55%, all P < 0.05). When the holding potential was set at +60 mV, the BK(Ca) current density of BNP group was (78.48 ± 5.86) pA/pF, which was significantly higher than control group [(53.84 ± 4.55) pA/pF, P < 0.05], which was equally reduced in the TEA group and TEA + BNP group [(28.80 ± 2.76) pA/pF and (30.60 ± 3.88) pA/pF respectively, all P < 0.05 vs. control group].</p><p><b>CONCLUSION</b>BNP could relax the porcine coronary arterial smooth muscles by increasing BK(Ca) current, and this effect is not mediated by NPR-C.</p>

Expressions of BNP and NPR-A in rat models of chronic nonbacterial prostatitis and their significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>We 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.</p><p><b>RESULTS</b>Higher 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.</p><p><b>CONCLUSION</b>BNP 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.</p>

Investigation of the Association between Normal-tension Glaucoma and Single Nucleotide Polymorphisms in Natriuretic Peptide Gene

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.

Vasonatrin peptide attenuates the enhancement of electrically-induced intracellular calcium transient by isoproterenol in rat cardiac myocytes / 生理学报

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.

Effect of vasonatrin peptide on the expression of C-type natriuretic peptide receptor in hypoxic rat hearts / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in hypoxic rat hearts.</p><p><b>METHODS</b>Rats 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>VNP 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.</p>

Neurohypophyseal hormones and atrial natriuretic peptide in the control of body fluid homeostasis

Mammals control the volume and osmolality of their body fluids by stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+-receptors (plasma osmolality or sodium concentration) and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrative response, which depends on the integrity of the anteroventral region of the third ventricle, e.g. organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. In addition, the paraventricular, supraoptic and suprachiasmatic nuclei are also important structures involved in hydromineral balance. The hypothalamo-neurohypophyseal system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and non-osmotic stimuli. The natriuretic factor in the heart, which is released by the distension of the atria, leading to natriuresis and a myorelaxing action on vascular smooth muscle, also contributes to the hydromineral balance. In addition to the natriuretic factor in the heart, the identification of a natriuretic factor in the central nervous system mediating natriuresis was also demonstrated by purification of hypothalamic extracts. Therefore, the presence of the natriuretic factor in the heart and in the central nervous system allowed the characterization of a neuroendocrine system controlling body fluid homeostasis.

Plasma Atrial Natriuretic Peptide Concentration after Birth in Low Birth Weight Neonates

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.

Neuroendocrine regulation of salt and water metabolism

Neurons which release atrial natriuretic peptide (ANPergic neurons) have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V) region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V) injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypotlalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume.

Membrane guanylate cyclase signal transduction system.

The suspect role of the receptor-mediated cyclic GMP signaling pathway was dispelled by the discovery of a membrane guanylate cyclase that was also an atrial natriuretic factor receptor. It is now established that the membrane guanylate cyclase transduction system is linked to the signaling of natriuretic factors, guanylin/enterotoxin, and emerging evidence suggests that a new neural tissue-specific subfamily of membrane guanylate cyclases exists whose mechanism of signal transduction is different from those of the other membrane cyclases. This review will briefly discuss the fascinating, albeit turbulent, history of this signal transduction field, which will be followed by its current status and finally the direction it is heading.

Isatin, a putative anxiogenic endocoid, induces memory dysfunction in rats.

Isatin (2,3-dioxoindole), one of the components of tribulin, which has been postulated to function as an endogenous marker of stress and anxiety, was shown to induce a dose-related attenuation of learning acquisition in an active avoidance test and inhibition of learning retention, or memory, in a step-down passive avoidance paradigm and transfer latency in an elevated plus-maze, in rats. Earlier studies have indicated that isatin functions as a 5-hydroxytryptamine (5-HT)3 receptor agonist in its anxiogenic activity in rats and is an antagonist at mammalian atrial natriuretic peptide (ANP) receptors. Since 5-HT3 receptor antagonists and centrally administered ANP have been shown to facilitate learning and memory, the observed memory dysfunction induced by isatin can be attributed to its receptor activity at 5-HT3 and ANP receptors. The investigation also indicates that anxiogenic agents are likely to disrupt memory functions.