The virtually mature BNP (BNP1-32) is a precursor for the more effective BNP1-30

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dc.contributor.authorSchwiebs, Anja
dc.contributor.authorWang, Yong
dc.contributor.authorMoore, Andrew M.
dc.contributor.authorZhu, Xudong
dc.contributor.authorPankow, Kristin
dc.contributor.authorSiems, Wolf-Eberhard
dc.contributor.authorWalther, Thomas
dc.contributor.funderDeutsche Forschungsgemeinschaften
dc.date.accessioned2019-12-03T13:02:20Z
dc.date.available2019-12-03T13:02:20Z
dc.date.issued2019-11-06
dc.date.updated2019-11-14T11:49:15Z
dc.description.abstractBackground and Purpose: The B‐type natriuretic peptide (BNP1‐32) exerts vasorelaxing and cardioprotective activity. BNP is used as a biomarker for the diagnosis of cardiopathological conditions and recombinant BNP1‐32 as a drug for the treatment of such. BNP1‐32 has a short half‐life time and thus, similar to other vasoactive peptides like angiotensin II and bradykinin, can be enzymatically truncated forming bioactive metabolites. We aimed to investigate the metabolism of BNP1‐32 in mouse lung, to identify potential new BNP metabolites and to disclose their biological activity compared to the BNP1‐32, in vitro and in vivo. Experimental Approach: Using High Performance Liquid Chromatography and Mass‐Spectrometry, we identified a new BNP metabolite, BNP1‐30, in the lung being generated by endothelin‐converting enzyme‐1. Key Results: BNP1‐30 is more efficient in stimulating the guanylyl cyclase receptor A (GC‐A) and, in contrast to BNP1‐32, is also able to profoundly stimulate the GC‐B. In vivo, BNP1‐30 reduced the mean arterial blood pressure of normotensive mice after acute infusion significantly more than BNP1‐32. In a model of severe hypertension, a 3‐day infusion of BNP1‐30 was able to reduce systolic blood pressure by 30 mmHg and to improve markers of heart failure, while BNP1‐32 was without significant effect. Conclusion and Implications: Our results suggest that BNP1‐32 is the precursor for the biologically more active BNP1‐30 leading to a fundamental extension of the natriuretic‐peptide system. Due to expanded activity, BNP1‐30 might be a promising treatment option for cardiovascular diseases. Furthermore, its potency as a new diagnostic marker of specific cardiac diseases should be evaluated.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (WA1441/18-2)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSchwiebs, A., Wang, Y., Moore, A. M., Zhu, X., Pankow, K., Siems, W.-E. and Walther, T. (2019) 'The virtually mature BNP (BNP1-32) is a precursor for the more effective BNP1-30', British Journal of Pharmacology. doi: 10.1111/bph.14890en
dc.identifier.doi10.1111/bph.14890en
dc.identifier.eissn1476-5381
dc.identifier.issn0007-1188
dc.identifier.journaltitleBritish Journal of Pharmacologyen
dc.identifier.urihttps://hdl.handle.net/10468/9305
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.relation.urihttps://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14890
dc.rights© 2019 The British Pharmacological Society. Published by John Wiley & Sons Inc. This is the peer reviewed version of the following article: Schwiebs, A., Wang, Y., Moore, A. M., Zhu, X., Pankow, K., Siems, W.-E. and Walther, T. (2019) 'The virtually mature BNP (BNP1-32) is a precursor for the more effective BNP1-30', British Journal of Pharmacology, doi: 10.1111/bph.14890, which has been published in final form at https://doi.org/10.1111/bph.14890. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.subjectCardiovascular diseaseen
dc.subjectHypertensionen
dc.subjectPharmacologyen
dc.subjectNatriuretic peptidesen
dc.subjectPeptide metabolismen
dc.titleThe virtually mature BNP (BNP1-32) is a precursor for the more effective BNP1-30en
dc.typeArticle (peer-reviewed)en
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