Disease relevance of Nppa

• 4. These findings suggest the existence of a blood pressure-dependent Nppa marker variant or a gene close to Nppa predisposing to spontaneous hypertension in the rat [1].
• In adult rats, ovariectomy decreases atrial ERalpha, the atria/body weight ratio, and atrial natriuretic peptide (ANP) transcription [2].
• We used freshly isolated rat hepatocytes to investigate the mechanisms by which ANP enhances hepatocyte resistance to hypoxia [3].
• Atrial natriuretic peptide (ANP) reduces ischemia and/or reperfusion damage in several organs, but the mechanisms involved are largely unknown [3].
• Effects of dehydration on endocrine regulation of the electrolyte and fluid balance and atrial natriuretic peptide-binding sites in perinatally malnourished adult male rats [4].

Psychiatry related information on Nppa

• Perinatal malnutrition also affects the responsiveness to water deprivation with alterations in both hypothalamic VP gene expression and regulation of ANP-binding sites [4].
• Atrial natriuretic factor (ANF) and its smaller congeners are produced and released from rat brains to regulate the cardiovascular system, drinking behavior, and neurohormone release at the central level [5].
• ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests) [6].
• 1. The influence of progesterone on the activity of atrial natriuretic factor (ANF) on rat myometrial motor activity was determined in vitro [7].
• Finally, ANP had no effect on eating or drinking after food deprivation, suggesting that the rats in the other experiments were not acutely incapacitated [8].

High impact information on Nppa

• Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats [9].
• Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP [10].
• Neonatal ventricular cells secrete ANF rapidly after synthesis and lack secretory granules [11].
• Atrial natriuretic peptide, acting through its second messenger guanosine 3',5'-cyclic monophosphate (cGMP), suppresses Na+ absorption across the renal inner-medullary collecting duct and increases urinary Na+ excretion [12].
• Atriopeptin, the atrial natriuretic peptide, is a circulating hormone that is released from the atria of mammalian hearts in response to volume expansion and acts upon the kidneys, adrenal glands and vasculature to regulate fluid and electrolyte homeostasis [13].

Chemical compound and disease context of Nppa

• After 72 h dehydration, control rats showed a significant rise in haematocrit, plasma osmolality, PRA, circulating levels of VP and aldosterone and VP gene expression in both PVN and SON but showed a decrease in plasma ANP levels [4].
• These data support the hypothesis that local ANP inhibits noradrenaline release in the AHA and thereby contributes to NaCl-sensitive hypertension in SHR [14].
• Cardiac fibrosis, fibronectin mRNA, and atrial natriuretic peptide mRNA were blocked by prazosin (7 mg.kg-1.d-1) [15].
• Effects of pertussis toxin (PT) treatment on atrial natriuretic peptide (ANP)-mediated inhibition of adenylate cyclase and amylase release were investigated in rat parotid gland [16].
• These results indicate that the guanylate cyclase-coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone [17].

Biological context of Nppa

• 3. A strong correlation was observed between the Nppa marker and blood pressure [1].
• A quantitative trait locus (QTL) for blood pressure on chromosome 5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM from the Nppa locus [1].
• Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker [1].
• In conclusion, ANP recruits 2 independent signal pathways, one mediated by cGMP and cGK and the other associated with G(i) proteins, phospholipase C, and PKC-delta [3].
• Downregulation of atrial natriuretic peptide ANP-C receptor is associated with alterations in G-protein expression in A10 smooth muscle cells [18].

Anatomical context of Nppa

• Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA [2].
• Mechanisms of hepatocyte protection against hypoxic injury by atrial natriuretic peptide [3].
• Inhibition of atrial natriuretic peptide (ANP) C receptor expression by antisense oligodeoxynucleotides in A10 vascular smooth-muscle cells is associated with attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase [19].
• In this study, we demonstrate that PAM co-localizes in atrial secretory granules with the storage form of atrial natriuretic peptide (pro-ANP, amino acids 1-126), a hormone involved in the maintenance of blood pressure and fluid homeostasis [20].
• 125I-ANP binding on adrenal ZG membranes was displaced by ANP(1-28) with an affinity (Kd) of 313 +/- 39 and 323 +/- 60 pM (NS) for pregnant and non-pregnant rats, respectively [21].

Associations of Nppa with chemical compounds

• Estrogen receptors activate atrial natriuretic peptide in the rat heart [2].
• The effects of ANP were mimicked by 8-bromo-guanosine 3', 5'-cyclic monophosphate (cGMP) and were associated with the activation of cGMP-dependent kinase (cGK), suggesting the involvement of guanylate cyclase-coupled natriuretic peptide receptor (NPR)-A/B ANP receptors [3].
• The p38 MAPK inhibitor SB203580 abolished ANP protection by reverting p38 MAPK-mediated regulation of Na(+) influx by the Na(+)/H(+) exchanger [3].
• In addition, angiotensin II- (Ang II-) mediated inhibition of adenylyl cyclase ( approximately 30%) was also abolished by C-ANP(4-23) treatment, indicating that the desensitization elicited by ANP was heterologous [18].
• Atrial natriuretic peptide (ANP) receptors A and B are guanylyl cyclase receptors, whereas ANP-C receptors are coupled to adenylyl cyclase through inhibitory guanine nucleotide (Gi) protein [18].

Physical interactions of Nppa

• The main effects were a significant rise in circulating levels of VP and aldosterone, and changes in density of adrenal ANP-binding sites and ANP-C receptor gene expression in both adrenals and kidneys [4].
• We have previously demonstrated that atrial natriuretic factor (ANF) binding consistent with the NPR-A receptor is significantly increased in FRTL-5 cells cultured in the presence of TSH [22].
• The 125I-ANF binding to retinal particulate preparations was not inhibited by 1 microM concentration of somatostatin, vasopressin, vasoactive intestinal peptide, adrenocorticotropin, thyrotropin releasing hormone, or leu-enkephalin [23].
• Cross-linking of atrial natriuretic peptide to binding sites in rat olfactory bulb membranes [24].
• Furthermore, chromatin immunoprecipitation analysis in H9c2 cells treated with phenylephrine showed that dHAND and myocyte enhancer factor 2C protein complex bind to the A/T sequence on atrial natriuretic peptide promoter [25].

Regulatory relationships of Nppa

• The ANP antagonist A71915 (10(-9) to 10(-6)) induced moderate dilation in renal vessels possibly due to some agonistic activity on NPR-B, ANP-induced preglomerular vasodilation was attenuated by A71915 (10(-6)) to 36 +/- 6% of the initial response, whereas efferent vasoconstriction was completely abolished (-4 +/- 4% of initial response) [26].
• These results suggest that central ANP stimulates pituitary GH secretion possibly by inhibiting SRIF release from the hypothalamus in the rat [27].
• Simvastatin was proved, in a dose-independent manner, to decrease cardiacmyocytes size as well as protein synthesis, and inhibit ANP mRNA synthesis and JAK-STAT protein expression induced by CT-1 in cardiacmyocytes.Conclusion: These results suggest that simvastatin can ameliorate cardiacmyocytes hypertrophyin vitrovia JAK-STAT signaling pathways [28].
• Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats [29].
• Atrial natriuretic peptide inhibits mitogen-activated protein kinase through the clearance receptor. Potential role in the inhibition of astrocyte proliferation [30].

Other interactions of Nppa

• ANP is not amidated by PAM, but rather is processed to its active form (amino acids 99-126) by the proteolytic cleavage of pro-ANP [20].
• Reciprocal paracrine pathways link atrial natriuretic peptide and somatostatin secretion in the antrum of the stomach [31].
• In cardiomyocytes, a distinct increase in ANP positivity was found, whereas PCNA positivity was very low [32].
• There was no correlation between the Nppa or Nppb genes or other markers in this region and either heart weight or left ventricular weight in F2 rats [1].
• Staurosporine and chelerythrine, protein kinase C (PKC) inhibitors at 1 and 100 nm, respectively, prevented the AngII-mediated desensitization of C-ANF 4-23-sensitive adenylyl cyclase [33].

Analytical, diagnostic and therapeutic context of Nppa

• Similar to the effects on ERalpha in the atria, ovariectomy lowered plasma ANP levels, and 17-beta-estradiol administration restored ANP in the plasma of ovariectomized rats [2].
• Plasma VP, ANP and aldosterone levels and PRA were determined by radioimmunoassay [4].
• ANP receptor gene expression was determined by Northern blot analysis [4].
• The locations of ANP and glial fibrillary acidic protein (GFAP) in normal and diabetic retinas were also established by immunohistochemistry [34].
• The expression of ANP and its receptors was analyzed by RT-PCR [35].

References