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Gene Review

Nppb  -  natriuretic peptide type B

Mus musculus

Synonyms: AA408272, BNF, BNP, Gamma-brain natriuretic peptide, Natriuretic peptides B
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Disease relevance of Nppb


High impact information on Nppb

  • These animals showed 10- to 100-fold increase in plasma BNP concentration accompanied by elevated plasma cyclic GMP concentration, and had significantly lower blood pressure than their nontransgenic littermates [4].
  • The mouse BNP gene was organized into three exons and two introns [4].
  • In transgenic (Tg) mice that overexpress BNP in response to hindlimb ischemia, neovascularization with appropriate mural cell coating was accelerated without edema or bleeding, and impaired angiogenesis by the suppression of nitric oxide production was effectively rescued [5].
  • In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in Nppb(-/-) mice, whereas no focal fibrotic changes are found in wild-type littermates (Nppb(+/+) mice) [1].
  • The half life of [125I]ANP in the circulation of homozygotes lacking NPRC is two-thirds longer than in the wild type, although plasma levels of ANP and BNP in heterozygotes and homozygotes are close to the wild type [6].

Chemical compound and disease context of Nppb

  • These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis [7].
  • We therefore compared angiotensin (Ang) II-induced cardiac hypertrophy and fibrosis in BNP-transgenic (Tg) mice, in which circulating BNP levels were elevated by increased secretion from the liver, and their non-Tg littermates [8].
  • Left ventricular hypertrophy was observed on echocardiography (1.25+/-0.05 mm vs. 0.86+/-0.02 mm in cTnI-wt, P<0.01), associated with a significant 4-fold increase in RNA markers of hypertrophy, ANF and BNP [9].
  • Myocyte cross-sectional area, a measure of hypertrophy, was decreased by 30% in the NS-398 versus vehicle group, but there was no effect on BNP mRNA [10].

Biological context of Nppb

  • Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth [2].
  • The ANP and BNP gene expressions are markedly augmented in ventricles of patients with a wide variety of cardiovascular diseases [11].
  • Such an autoregulatory pathway may represent an important physiological homeostatic mechanism and link the paracrine activity of NO and CNP with the endocrine functions of ANP and BNP in the regulation of vascular tone and blood pressure [12].
  • It has been demonstrated that the ANP and BNP genes are tightly linked on mouse chromosome 4 and on the distal short arm of human chromosome 1 [11].
  • By polymerase chain reaction, we isolated an approximately 11-kb human genomic DNA fragment containing the third exon of the BNP gene and the first and second exons of the ANP gene [11].

Anatomical context of Nppb


Associations of Nppb with chemical compounds


Physical interactions of Nppb


Regulatory relationships of Nppb


Other interactions of Nppb

  • Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide [2].
  • The family of rGCs is rapidly expanding, and it is plausible that there might be additional, as yet undiscovered, rGCs whose function is to provide alternative signalling pathways for one or both of these peptides, particularly given the low affinity of NPRA for BNP [13].
  • In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP-/- mice examined, accompanied by further increase of mRNA expression of TGF-beta3 and Col alpha1(I) [3].
  • CONCLUSIONS: Increased BNP-mRNA levels in hypertensive ANG-overexpressing mice and decreased BNP in hypotensive AT1-deficient animals suggest that this mRNA expression is blood pressure-dependent [24].
  • However, the observed alterations of fibrosis and the unchanged BNP in hypotensive ANG knockouts and impaired BNP-mRNA expression in normotensive AT2-deficient mice demonstrate a direct interaction of the RAS and NPS that is fibrosis- rather than blood pressure-dependent [24].

Analytical, diagnostic and therapeutic context of Nppb


  1. Cardiac fibrosis in mice lacking brain natriuretic peptide. Tamura, N., Ogawa, Y., Chusho, H., Nakamura, K., Nakao, K., Suda, M., Kasahara, M., Hashimoto, R., Katsuura, G., Mukoyama, M., Itoh, H., Saito, Y., Tanaka, I., Otani, H., Katsuki, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. Suda, M., Ogawa, Y., Tanaka, K., Tamura, N., Yasoda, A., Takigawa, T., Uehira, M., Nishimoto, H., Itoh, H., Saito, Y., Shiota, K., Nakao, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart. Ogawa, Y., Tamura, N., Chusho, H., Nakao, K. Can. J. Physiol. Pharmacol. (2001) [Pubmed]
  4. Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene. Ogawa, Y., Itoh, H., Tamura, N., Suga, S., Yoshimasa, T., Uehira, M., Matsuda, S., Shiono, S., Nishimoto, H., Nakao, K. J. Clin. Invest. (1994) [Pubmed]
  5. Significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration. Yamahara, K., Itoh, H., Chun, T.H., Ogawa, Y., Yamashita, J., Sawada, N., Fukunaga, Y., Sone, M., Yurugi-Kobayashi, T., Miyashita, K., Tsujimoto, H., Kook, H., Feil, R., Garbers, D.L., Hofmann, F., Nakao, K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. Matsukawa, N., Grzesik, W.J., Takahashi, N., Pandey, K.N., Pang, S., Yamauchi, M., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Which of the cardiac natriuretic peptides is most effective for the treatment of congestive heart failure, renal failure and cancer? Vesely, D.L. Clin. Exp. Pharmacol. Physiol. (2006) [Pubmed]
  8. Angiotensin II-induced ventricular hypertrophy and extracellular signal-regulated kinase activation are suppressed in mice overexpressing brain natriuretic peptide in circulation. Takahashi, N., Saito, Y., Kuwahara, K., Harada, M., Kishimoto, I., Ogawa, Y., Kawakami, R., Nakagawa, Y., Nakanishi, M., Nakao, K. Hypertens. Res. (2003) [Pubmed]
  9. Molecular insights from a novel cardiac troponin I mouse model of familial hypertrophic cardiomyopathy. Tsoutsman, T., Chung, J., Doolan, A., Nguyen, L., Williams, I.A., Tu, E., Lam, L., Bailey, C.G., Rasko, J.E., Allen, D.G., Semsarian, C. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  10. Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse. LaPointe, M.C., Mendez, M., Leung, A., Tao, Z., Yang, X.P. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  11. Two cardiac natriuretic peptide genes (atrial natriuretic peptide and brain natriuretic peptide) are organized in tandem in the mouse and human genomes. Tamura, N., Ogawa, Y., Yasoda, A., Itoh, H., Saito, Y., Nakao, K. J. Mol. Cell. Cardiol. (1996) [Pubmed]
  12. Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling. Madhani, M., Scotland, R.S., MacAllister, R.J., Hobbs, A.J. Br. J. Pharmacol. (2003) [Pubmed]
  13. Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide. Goy, M.F., Oliver, P.M., Purdy, K.E., Knowles, J.W., Fox, J.E., Mohler, P.J., Qian, X., Smithies, O., Maeda, N. Biochem. J. (2001) [Pubmed]
  14. NPR-A-Deficient mice show increased susceptibility to hypoxia-induced pulmonary hypertension. Zhao, L., Long, L., Morrell, N.W., Wilkins, M.R. Circulation (1999) [Pubmed]
  15. The sites of gene expression of atrial, brain, and C-type natriuretic peptides in mouse fetal development: temporal changes in embryos and placenta. Cameron, V.A., Aitken, G.D., Ellmers, L.J., Kennedy, M.A., Espiner, E.A. Endocrinology (1996) [Pubmed]
  16. Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Steinhelper, M.E. Circ. Res. (1993) [Pubmed]
  17. C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells. Fowkes, R.C., Forrest-Owen, W., McArdle, C.A. J. Endocrinol. (2000) [Pubmed]
  18. Apparent B-type natriuretic peptide selectivity in the kidney due to differential processing. Kishimoto, I., Hamra, F.K., Garbers, D.L. Can. J. Physiol. Pharmacol. (2001) [Pubmed]
  19. Receptor-mediated stimulatory effect of atrial natriuretic factor, brain natriuretic peptide, and C-type natriuretic peptide on testosterone production in purified mouse Leydig cells: activation of cholesterol side-chain cleavage enzyme. Khurana, M.L., Pandey, K.N. Endocrinology (1993) [Pubmed]
  20. Essential biochemistry and physiology of (NT-pro)BNP. Hall, C. Eur. J. Heart Fail. (2004) [Pubmed]
  21. Molecular biology and biochemistry of natriuretic peptide family. Ogawa, Y., Itoh, H., Nakao, K. Clin. Exp. Pharmacol. Physiol. (1995) [Pubmed]
  22. Haploinsufficiency of the cardiac transcription factor Nkx2-5 variably affects the expression of putative target genes. Jay, P.Y., Rozhitskaya, O., Tarnavski, O., Sherwood, M.C., Dorfman, A.L., Lu, Y., Ueyama, T., Izumo, S. FASEB J. (2005) [Pubmed]
  23. AlbuBNP, a recombinant B-type natriuretic peptide and human serum albumin fusion hormone, as a long-term therapy of congestive heart failure. Wang, W., Ou, Y., Shi, Y. Pharm. Res. (2004) [Pubmed]
  24. Fibrosis rather than blood pressure determines cardiac BNP expression in mice. Walther, T., Klostermann, K., Heringer-Walther, S., Schultheiss, H.P., Tschöpe, C., Stepan, H. Regul. Pept. (2003) [Pubmed]
  25. Expression of B-type natriuretic peptide in atrial natriuretic peptide gene disrupted mice. Tse, M.Y., Watson, J.D., Sarda, I.R., Flynn, T.G., Pang, S.C. Mol. Cell. Biochem. (2001) [Pubmed]
  26. Natriuretic peptide expression in the heart of the TTR-ANP transgenic mouse-Comparison to the normal heart. Lundberg, S., Hansson, M. Microsc. Res. Tech. (2005) [Pubmed]
  27. Natriuretic peptides in ectopic myocardial tissues originating from mouse embryonic stem cells. Johkura, K., Cui, L., Yue, F., Nitta, K., Takei, S., Okouchi, Y., Asanuma, K., Ogiwara, N., Sasaki, K. Microsc. Res. Tech. (2005) [Pubmed]
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