{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:50:09Z","timestamp":1747183809427,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WA1441\/18\u20102"],"award-info":[{"award-number":["WA1441\/18\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The B\u2010type natriuretic peptide (BNP1\u201032) exerts vasorelaxing and cardioprotective activity. BNP is used as a biomarker for the diagnosis of cardiopathological conditions and recombinant BNP1\u201032 as a drug for the treatment of such. BNP1\u201032 has a short half\u2010life 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\u201032 in the mouse lung, to identify potential new BNP metabolites and to disclose their biological activity compared to the BNP1\u201032, <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Using HPLC and MS, we identified a new BNP metabolite, BNP1\u201030, in the lung being generated by endothelin\u2010converting enzyme\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>BNP1\u201030 is more efficient in stimulating the guanylyl cyclase (GC) receptor A and, in contrast to BNP1\u201032, is also able to profoundly stimulate the GC\u2010B. <jats:italic>In vivo<\/jats:italic>, BNP1\u201030 reduced the mean arterial BP of normotensive mice after acute infusion significantly more than BNP1\u201032. In a model of severe hypertension, a 3\u2010day infusion of BNP1\u201030 was able to reduce systolic BP by 30 mmHg and to improve markers of heart failure, while BNP1\u201032 was without significant effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our results suggest that BNP1\u201032 is the precursor for the biologically more active BNP1\u201030 leading to a fundamental extension of the natriuretic peptide system. Due to expanded activity, BNP1\u201030 might be a promising treatment option for cardiovascular diseases. Furthermore, its potency as a new diagnostic marker of specific cardiac diseases should be evaluated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14890","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T11:20:10Z","timestamp":1573039210000},"page":"1424-1433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The virtually mature B\u2010type natriuretic peptide (BNP1\u201032) is a precursor for the more effective BNP1\u201030"],"prefix":"10.1111","volume":"177","author":[{"given":"Anja","family":"Schwiebs","sequence":"first","affiliation":[{"name":"Department of Experimental Cardiology, Excellence Cluster Cardio\u2010Pulmonary System Justus\u2010Liebig\u2010Universit\u00e4t Giessen  Giessen Germany"},{"name":"Institute of General Pharmacology and Toxicology Hospital of the Goethe University Frankfurt  Frankfurt 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