Epithelium integrity is crucial for the relaxant activity of brain natriuretic peptide in human isolated bronchi

Maria G. Matera, Luigino Calzetta, Daniela Passeri, Francesco Facciolo, Erino A. Rendina, Clive Page, Mario Cazzola, Augusto Orlandi

Research output: Contribution to journalArticlepeer-review


BACKGROUND AND PURPOSE Brain natriuretic peptide (BNP) plays an important role in several biological functions, including bronchial relaxation. Here, we have investigated the role of BNP and its cognate receptors in human bronchial tone. EXPERIMENTAL APPROACH Effects of BNP on responses to carbachol and histamine were evaluated in non-sensitized, passively sensitized, epithelium-intact or denuded isolated bronchi and in the presence of methoctramine, N ω-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine. Natriuretic peptide receptors (NPRs) were investigated by immunohistochemistry, RT-PCR and real-time PCR. Release of NO and acetylcholine from bronchial tissues and cultured BEAS-2B bronchial epithelial cells was also investigated. KEY RESULTS BNP reduced contractions mediated by carbachol and histamine, with decreased E max (carbachol: 22.7 ± 4.7%; histamine: 59.3 ± 1.8%) and increased EC 50 (carbachol: control 3.33 ± 0.88 μM, BNP 100 ± 52.9 μM; histamine: control 16.7 ± 1.7 μM, BNP 90 ± 30.6 μM); BNP was ineffective in epithelium-denuded bronchi. Among NPRs, only atrial NPR (NPR1) transcripts were detected in bronchial tissue. Bronchial NPR1 immunoreactivity was detected in epithelium and inflammatory cells but faint or absent in airway smooth muscle cells. NPR1 transcripts in bronchi increased after incubation with BNP, but not after sensitization. Methoctramine and quinine abolished BNP-induced relaxant activity. The latter was associated with increased bronchial mRNA for NO synthase and NO release, inhibited by L-NAME and aminoguanidine. In vitro, BNP increased acetylcholine release from bronchial epithelial cells, whereas NO release was unchanged. CONCLUSIONS AND IMPLICATIONS Epithelial cells mediate the BNP-induced relaxant activity in human isolated bronchi.

Original languageEnglish
Pages (from-to)1740-1754
Number of pages15
JournalBritish Journal of Pharmacology
Issue number8
Publication statusPublished - Aug 2011


  • acetylcholine
  • brain natriuretic peptide
  • bronchodilatation
  • inducible NOS
  • natriuretic peptide receptor A
  • nitric oxide

ASJC Scopus subject areas

  • Pharmacology


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