Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide: Impact of preserved lung function and structure

Dorottya Czo¨vek, F. Peták, Yves Donati, Xavier Belin, Jean Claude Pache, Constance Barazzone Argiroffo, Walid Habre

Research output: Contribution to journalArticle

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Abstract

Objective: Hyperoxia exposure leads to the development of lung injury and bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We aimed at characterizing whether the stimulation of the NO pathway by sildenafil or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced development of BHR. The respective roles of the preserved lung volume and alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of these treatments in the diminished lung responsiveness were also characterized. Materials and methods: Immature (28-day-old) rats were exposed for 72 hours to room air (Group C), hyperoxia (>95%, Group HC), or hyperoxia with the concomitant administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil (Group HS). Following exposure, the end-expiratory lung volume (EELV) was assessed plethysmographically. Airway and respiratory tissue mechanics were measured under baseline conditions and following incremental doses of methacholine to assess BHR. Inflammation was assessed by analyzing the bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses were used to characterize the apoptotic and structural changes in the lungs. Results: The BHR, the increased EELV, the aberrant alveolarization, and the infiltration of inflammatory cells into the BALF that developed in Group HC were all suppressed significantly by VIP or sildenafil treatment. The number of apoptotic cells increased significantly in Group HC, with no evidence of statistically significant effects on this adverse change in Groups HS and HV. Conclusions: These findings suggest that stimulating the NO pathway by sildenafil and VIP exert their beneficial effect against hyperoxia-induced BHR via preserving normal EELV, inhibiting airway inflammation and preserving the physiological lung structure, whereas the antiapoptotic potential of these treatments were not apparent in this process.

Original languageEnglish
Article number81
JournalRespiratory Research
Volume15
Issue number1
DOIs
Publication statusPublished - Aug 13 2014

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Bronchial Hyperreactivity
Hyperoxia
Vasoactive Intestinal Peptide
Lung
Nitric Oxide
Bronchoalveolar Lavage Fluid
Inflammation
Respiratory Mechanics
Methacholine Chloride
Lung Injury
Sildenafil Citrate
Anti-Inflammatory Agents
Therapeutics
Cell Count
Air

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide : Impact of preserved lung function and structure. / Czo¨vek, Dorottya; Peták, F.; Donati, Yves; Belin, Xavier; Pache, Jean Claude; Barazzone Argiroffo, Constance; Habre, Walid.

In: Respiratory Research, Vol. 15, No. 1, 81, 13.08.2014.

Research output: Contribution to journalArticle

Czo¨vek, Dorottya ; Peták, F. ; Donati, Yves ; Belin, Xavier ; Pache, Jean Claude ; Barazzone Argiroffo, Constance ; Habre, Walid. / Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide : Impact of preserved lung function and structure. In: Respiratory Research. 2014 ; Vol. 15, No. 1.
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abstract = "Objective: Hyperoxia exposure leads to the development of lung injury and bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We aimed at characterizing whether the stimulation of the NO pathway by sildenafil or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced development of BHR. The respective roles of the preserved lung volume and alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of these treatments in the diminished lung responsiveness were also characterized. Materials and methods: Immature (28-day-old) rats were exposed for 72 hours to room air (Group C), hyperoxia (>95{\%}, Group HC), or hyperoxia with the concomitant administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil (Group HS). Following exposure, the end-expiratory lung volume (EELV) was assessed plethysmographically. Airway and respiratory tissue mechanics were measured under baseline conditions and following incremental doses of methacholine to assess BHR. Inflammation was assessed by analyzing the bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses were used to characterize the apoptotic and structural changes in the lungs. Results: The BHR, the increased EELV, the aberrant alveolarization, and the infiltration of inflammatory cells into the BALF that developed in Group HC were all suppressed significantly by VIP or sildenafil treatment. The number of apoptotic cells increased significantly in Group HC, with no evidence of statistically significant effects on this adverse change in Groups HS and HV. Conclusions: These findings suggest that stimulating the NO pathway by sildenafil and VIP exert their beneficial effect against hyperoxia-induced BHR via preserving normal EELV, inhibiting airway inflammation and preserving the physiological lung structure, whereas the antiapoptotic potential of these treatments were not apparent in this process.",
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