The virtually mature B-type natriuretic peptide (BNP1-32) is a precursor for the more effective BNP1-30.

Abstract

Background and PurposeThe 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 ApproachUsing HPLC and MS, we identified a new BNP metabolite, BNP1‐30, in the lung being generated by endothelin‐converting enzyme‐1.Key ResultsBNP1‐30 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 ImplicationsOur 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.