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. 2013 Jul 19;15(4):169–178. doi: 10.1179/174329210X12650506623609

Inducible NOS inhibitor 1400W reduces hypoxia/re-oxygenation injury in rat lung

Alma Rus 1, Lourdes Castro 1, Maria Luisa del Moral 1, Ángeles Peinado 2
PMCID: PMC7067322  PMID: 20663293

Abstract

Nitric oxide (NO•) from inducible NO• synthase (iNOS) has been reported to either protect against, or contribute to, hypoxia/re-oxygenation lung injury. The present work aimed to clarify this double role in the hypoxic lung. With this objective, a follow-up study was made in Wistar rats submitted to hypoxia/re-oxygenation (hypoxia for 30 min; re-oxygenation of 0 h, 48 h, and 5 days), with or without prior treatment with the selective iNOS inhibitor 1400W (10 mg/kg). NO• levels (NOx), lipid peroxidation, apoptosis, and protein nitration were analysed. This is the first time-course study which investigates the effects of 1400W during hypoxia/re-oxygenation in the rat lung. The results showed that the administration of 1400W lowered NOx levels in all the experimental groups. In addition, lipid peroxidation, the percentage of apoptotic cells, and nitrated protein expression fell in the late post-hypoxia period (48 h and 5 days). Our results reveal that the inhibition of iNOS in the hypoxic lung reduced the damage observed before the treatment with 1400W, suggesting that iNOS-derived NO• may exert a negative effect on this organ during hypoxia/re-oxygenation. These findings are notable, since they indicate that any therapeutic strategy aimed at controlling excess generation of NO• from iNOS may be useful in alleviating NO•-mediated adverse effects in hypoxic lungs.

Keywords: 1400W, HYPOXIA, NITRIC OXIDE, INDUCIBLE NITRIC OXIDE SYNTHASE, RE-OXYGENATION PERIOD, APOPTOSIS, LIPID PEROXIDATION, NITROTYROSINE FORMATION

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