Expression of natriuretic peptide receptor A in the developing retina of the mouse / 解剖学报

Objective Our purpose is to investigate the expression of natriuretic peptide receptor A (NPR-A) in the retina and to understand the NPR-A’ s functions during the mouse development .Methods Mice eyes were harvested from E16 ( embryonic day 16 ) to P90 ( postnatal day 90 ) . Total of 127 eyes were used in the study . Immunohistochemistries of NPR-A were carried out .Results During development , NPR-A was widely expressed in the retinal neurons .In the outer nuclear layer , NPR-A began to appear in the inner and outer projections of cone and rod cells at P7, but decreased at P14.From P30 afterward, it continued to express weakly .In the inner nuclear layer , NPR-A expressed in the dendrites of bipolar cells weakly from P 7 to adulthood , whereas no expression in horizontal cells .In the ganglion cell layer, NPR-A started highly to express in the ganglion cell bodies at E 16, and in the meantime, in the nerve fiber layer , ganglion cell axons , NPR-A was expressed highly from embryonic to adult .In the inner and outer plexiform layers, NPR-A was highly expressed at P14, but decreased gradually after P30.In addition, NPR-A also widely expressed in the inner protrusions of Müller cells.Conclusion NPR-A participates in the development of the retina , and may be the key molecule in the developing retinal neurons .Moreover, it plays an important regulatory role in the functional activity of Müller cells .

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.

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.

Altered Atrial Natriuretic Peptide System in the Kidney of Bilateral Obstructive Uropathic Rats / 대한신장학회잡지

BACKGROUND: Although being associated with an elevated plasma atrial natriuretic peptide(ANP), its precise role in the postobstructive diuresis has not been fully understood. Evidence has been provided suggesting that the locally-synthesized ANP in the kidney contributes to the regulation of urinary sodium excretion. The present study was aimed to investigate whether an altered regulation of local ANP system is involved in the postobstructive diuresis. METHODS: Male Sprague-Dawley rats were used. Both proximal ureters were ligated for 48 hours, after which the kidneys were taken without releasing the ligature, being designated as bilateral ureteral obstruction(BUO) group; or the ligature was released and 4 or 24 hr later, urinary data were collected, being designated as BUR-4 or BUR-24, respectively. Sham operated rats were used as control. Plasma ANP levels were determined by radioimmunoassay. The expression of ANP and natriuretic peptide receptor(NPR)-A mRNAs was determined by reverse transcription-polymerase chain reaction(RT-PCR). To further examine whether the altered renal ANP system, if any, was associated with an altered biological effects of guanylyl cyclase, ANP-stimulated cGMP accumulation was determined in membrane preparations of the glomeruli and papillae by radioimmunoassay. RESULTS: The plasma ANP level was increased in BUO group compared with that in the control(260.5+/-32.5 vs. 133.3+/-23.5pg/mL, p<0.05), decreased in BUR-4 group(3.6+/-0.5 vs. 143.5+/-42.8pg/mL, p<0.01), while not significantly different in BUR-24 group. In BUR-4. the urinary flow rate increased compared with that in the control(1598+/-370 vs. 215+/-34 microL/hr, p<0.01), along with increases of FENa(11.5+/-4.1 vs. 0.25+/-0.02%, p<0.05) and UNaV (153.7+/-23.7 vs. 36.5+/-9.3microEq/hr, p<0.01). In BUR-24, the urinary parameters were normalized. Renal tissue expression of ANP mRNA was increased in BUO as well as in BUR-4, while not changed in BUR-24. NPR-A mRNA expression was decreased in the kidney of BUO. The ANP-stimulated accumulation of cGMP in the isolated glomeruli and papillae in BUO was significantly reduced. The guanylyl cyclase activities were partly recovered in BUR-4 and completely in BUR-24. CONCLUSION: An enhanced local activity of ANP in the kidney may be causally related to the postobstructive diuresis.