Nitric Oxide Prevents Alveolar Senescence and Emphysema in a Mouse Model

作者：Boe Amanda E; Eren Mesut; Morales Nebreda Luisa; Murphy Sheila B; Budinger G R Scott; Mutlu Goekhan M; Miyata Toshio; Vaughan Douglas E^*

来源：PLos One, 2015, 10(3): e0116504.

DOI：10.1371/journal.pone.0116504

N-omega-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-NAME-induced 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.

• 出版日期2015-3-10
• 单位西北大学