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The virtually mature B‐type natriuretic peptide (BNP1‐32) is a precursor for the more effective BNP1‐30
Author(s) -
Schwiebs Anja,
Wang Yong,
Moore Andrew M.,
Zhu Xudong,
Pankow Kristin,
Siems WolfEberhard,
Walther Thomas
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14890
Subject(s) - natriuretic peptide , in vivo , pharmacology , metabolite , bradykinin , brain natriuretic peptide , biological activity , medicine , renin–angiotensin system , receptor , heart failure , ex vivo , angiotensin ii , endocrinology , chemistry , biochemistry , in vitro , blood pressure , biology , microbiology and biotechnology
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 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 the 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 HPLC and MS, 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 (GC) receptor A and, in contrast to BNP1‐32, is also able to profoundly stimulate the GC‐B. In vivo , BNP1‐30 reduced the mean arterial BP 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 BP by 30 mmHg and to improve markers of heart failure, while BNP1‐32 was without significant effect. Conclusions 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.