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

4 Scopus citations

Abstract

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 (US)
Article numbere0116504
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • General

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