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Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats
Hen I Lin1, Shi Jye Chu, Kang Hsu
1Department of Internal Medicine, Catholic Cardinal Tien Hospital, Fu-Jen Catholic University, Taipei Hsien, Taiwan, ROC.
Abstract:
In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO.
Insights
Inhaled nitric oxide (NO) worsened acute lung injury in rats when induced by phorbol myristate acetate (PMA). However, Nomega-nitro-L-arginine methyl ester (L-NAME) mitigated this NO-induced exacerbation.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Pharmacology
Background:
- Acute lung injury (ALI) is a critical condition characterized by increased pulmonary vascular permeability.
- Phorbol myristate acetate (PMA) is a known inducer of ALI in experimental models.
- Nitric oxide (NO) plays complex roles in inflammation and vascular function.
Purpose of the Study:
- To investigate the effect of inhaled nitric oxide (NO) on acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in an isolated rat lung model.
- To determine the role of NO in modulating PMA-induced pulmonary vascular injury.
Main Methods:
- Acute lung injury was induced in isolated rat lungs using phorbol myristate acetate (PMA).
- Animals were pretreated with inhaled nitric oxide (NO) or co-administered with Nomega-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor.
- Key parameters assessed included microvascular permeability (capillary filtration coefficient, Kfc), lung weight gain, and bronchoalveolar lavage fluid protein concentration.
Main Results:
- PMA administration successfully induced ALI, increasing microvascular permeability, lung weight, and lavage fluid protein.
- Inhaled NO (30 ppm) significantly exacerbated PMA-induced ALI, worsening lung injury parameters except for pulmonary arterial pressure.
- Nomega-nitro-L-arginine methyl ester (L-NAME) attenuated the detrimental effects of inhaled NO on PMA-induced lung injury.
Conclusions:
- Inhaled nitric oxide significantly exacerbates acute lung injury induced by PMA in a rat model.
- The findings suggest a pro-inflammatory or damaging role for inhaled NO in this specific ALI context.
- Inhibition of NO synthesis with L-NAME can mitigate the exacerbating effects of inhaled NO on lung injury.
