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

Loading...
Thumbnail Image
Date
2019-11-06
Authors
Schwiebs, Anja
Wang, Yong
Moore, Andrew M.
Zhu, Xudong
Pankow, Kristin
Siems, Wolf-Eberhard
Walther, Thomas
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons, Inc.
Published Version
Research Projects
Organizational Units
Journal Issue
Abstract
Background 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.
Description
Keywords
Cardiovascular disease , Hypertension , Pharmacology , Natriuretic peptides , Peptide metabolism
Citation
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
Copyright
© 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.