natriuretic-peptide--brain and Bronchial-Hyperreactivity

Topics: Bronchial Hyperreactivity; Cardiac Catheterization; Echocardiography; Electrocardiography; Exercise Test; France; Humans; Natriuretic Peptide, Brain; Oscillometry; Oximetry; Plethysmography; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Respiratory Muscles; Severity of Illness Index; Surveys and Questionnaires

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 of ASM cells was microscopically assessed in vitro in the presence of 1 μM BNP or with supernatant from human bronchial epithelial (BEAS-2B) cells pretreated with 1 μM 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.

Topics: Acetylcholine; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; Case-Control Studies; Cell Communication; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Dose-Response Relationship, Drug; Epithelial Cells; Humans; Muscle, Smooth; Myocytes, Smooth Muscle; Myosin-Light-Chain Phosphatase; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase Type II; Receptor, Muscarinic M2; Respiratory Mucosa; Signal Transduction

Brain natriuretic peptide (BNP) relaxes guinea pig tracheal smooth muscle in vitro and is effective in preventing ovalbumin-induced bronchoconstriction and microvascular leakage in guinea pigs in vivo. Nonetheless, published studies on BNP in human airways in vitro are still lacking in the literature. The aim of this study was to investigate the effect of BNP in isolated human bronchi. The relaxant effect of BNP (1 nM to 10 microM) was assessed in nonsensitized and in passively sensitized human bronchial airways pre-contracted with submaximal concentration (EC(70)) of carbachol or histamine. At the end of the experiment, papaverine (500 microM) was then added. BNP induced a weak relaxant activity on carbachol-contracted bronchi in nonsensitized (relaxation: 4.23+/-0.51%) and passively sensitized bronchi (relaxation: 11.31+/-2.22%). On the other hand, BNP induced a relaxant activity on His-contracted bronchi in nonsensitized (relaxation: 42.52+/-9.03%) and in passively sensitized (relaxation: 60.57+/-9.58%). All these findings are a clear documentation of the modest relaxant role of BNP in asthma and, likely, COPD.

Topics: Bronchi; Bronchial Hyperreactivity; Carbachol; Histamine; Humans; Immunization, Passive; In Vitro Techniques; Muscle Contraction; Natriuretic Peptide, Brain; Nicotinic Agonists; Papaverine; Vasodilator Agents