Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.
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.
Lin
Hen I
HI
Department of Internal Medicine, Catholic Cardinal Tien Hospital, Fu-Jen Catholic University, Taipei Hsien, Taiwan, ROC.
Chu
Shi Jye
SJ
Hsu
Kang
K
Wang
David
D
D000280:Administration, Inhalation; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004347:Drug Interactions; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D002273:Carcinogens; D009569:Nitric Oxide; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester