Combined effects of nitric oxide and hyperoxia on surfactant function and pulmonary inflammation.
NO and its derivative ONOO- are potent free radicals that can cause cell damage, especially in the presence of O2. To determine the potential pulmonary toxicities of nitric oxide (NO) and peroxynitrite (ONOO-) in vitro, Survanta (2.5 mg/ml) was exposed to ONOO- (0.3-8 mM) in the presence of two different buffering systems (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid and phosphate buffer) and minimum surface tension (MST) was determined with an oscillating bubble surfactometer. Significant increases in MST were seen only with exposure to 8 mM ONOO-, indicating that in vitro, high concentrations of ONOO- can inhibit natural surfactant function. The in vivo effects of NO and hyperoxia were then studied in four groups of newborn piglets ventilated for 48 h with 21% O2, 100% O2, 21% O2 and 100 ppm NO, or with 90% O2 and 100 ppm NO. Five animals served as an untreated control group. Bronchoalveolar lavage fluid (BAL) obtained at 48 h was subjected to centrifugation and the surfactant pellet was reconstituted to 5 mg phospholipid/ml. Significant increases in MST were seen in surfactant from piglets ventilated with NO and 90% O2, compared with either untreated controls or piglets ventilated with 21% O2 for 48 h (P < 0.05, analysis of variance). Significant increases in neutrophil chemotactic activity (NCA) of BAL were also found in the NO and O2 group (P < 0.05), with significant positive interaction between NO and O2 found (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000831:Animals, Newborn; D001688:Biological Products; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002021:Buffers; D018496:Hyperoxia / Q000150:complications* / Q000503:physiopathology*; D008706:Methemoglobin / Q000032:analysis; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D010100:Oxygen; D011014:Pneumonia / Q000139:chemically induced* / Q000209:etiology* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000502:physiology*; D012119:Respiration; D013500:Surface Tension; D013552:Swine
D001688:Biological Products; D015415:Biomarkers; D002021:Buffers; D009566:Nitrates; D011663:Pulmonary Surfactants; C039642:peroxynitric acid; D009569:Nitric Oxide; D008706:Methemoglobin; C072197:beractant; D010100:Oxygen