Nitric oxide prevents alveolar senescence and emphysema in a mouse model

Amanda E. Boe, Mesut Eren, Luisa Morales-Nebreda, Sheila B. Murphy, G. R. Scott Budinger, Gökhan M. Mutlu, Toshio Miyata, Douglas E. Vaughan

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Nω-nitro-L-arginine methyl ester (L-NAME) treatment induces arteriosclerosis and vascular senescence. Here, we report that the systemic inhibition of nitric oxide (NO) production by L-NAME causes pulmonary emphysema. L-NAME-treated lungs exhibited both the structural (alveolar tissue destruction) and functional (increased compliance and reduced elastance) characteristics of emphysema development. Furthermore, we found that L-NAMEinduced emphysema could be attenuated through both genetic deficiency and pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1). Because PAI-1 is an important contributor to the development of senescence both in vitro and in vivo, we investigated whether L-NAME-induced senescence led to the observed emphysematous changes. We found that L-NAME treatment was associated with molecular and cellular evidence of premature senescence in mice, and that PAI-1 inhibition attenuated these increases. These findings indicate that NO serves to protect and defend lung tissue from physiological aging.

Original languageEnglish
Article numbere0116504
JournalPLoS ONE
Issue number3
Publication statusPublished - 2015 Mar 1


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