Brain Natriuretic Peptide Protects against Hyperresponsiveness of Human Asthmatic Airway Smooth Muscle via an Epithelial Cell-Dependent Mechanism

Luigino Calzetta, Daniela Passeri, Varsha Kanabar, Paola Rogliani, Clive Page, Mario Cazzola*, Maria Gabriella Matera, Augusto Orlandi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Brain natriuretic peptide (BNP) relaxes airways by activating natriuretic peptide receptor-A and elevating cyclic guanosine monophosphate. BNP is more effective in passively sensitized human bronchi compared with control airways. The molecular and cellular patterns involved in this signaling are unknown. The aim of this study was to investigate the influence of BNP on airway smooth muscle (ASM) cells obtained from donors with asthma and healthy donors and to identify the mechanisms involved in BNP-mediated relaxation. The contractile response ofASMcells was microscopically assessed in vitro in the presence of 1 mM BNP or with supernatant from human bronchial epithelial (BEAS-2B) cells pretreated with 1 mM BNP. We investigated the role of muscarinic M2 receptors and inducible nitric oxide synthase (iNOS), quantified the release of acetylcholine and nitric oxide (NO), and assessed the gene/protein expression of iNOS and myosin phosphatase target subunit 1 (MYPT1). Supernatant from BEAS-2B cells treated with BNP reduced the hyperreactivity of asthmatic ASM cells by shifting the potency of histamine by 1.19-fold but had no effect in healthy ASM cells. BNP was not effective directly on ASM cells. Blocking muscarinic M2-receptors and iNOS abolished the protective role of supernatant from BEAS-2B treated with BNP. BNP stimulated the release of acetylcholine (210.7 +/- 11.1%) from BEAS-2B cells that in turn increased MYPT1 and iNOS gene/protein expression and enhanced NO levels in asthmatic ASM supernatant (35.0 +/- 13.0%). This study provides evidence that BNP protects against bronchial hyperresponsiveness via an interaction between respiratory epithelium and ASM in subjects with asthma.

Original languageEnglish
Article numberN/A
Pages (from-to)493-501
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number3
Publication statusPublished - Mar 2014


  • brain natriuretic peptide
  • bronchial hyperresponsiveness
  • airway smooth muscle
  • airway epithelium
  • nitric oxide


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