title: Nitric oxide prevents alveolar senescence and emphysema in a mouse model.
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-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.
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America; Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Boe
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Mesut
authors.initials: M
authors.lastname: Eren
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales-Nebreda
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America; Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Sheila B
authors.initials: SB
authors.lastname: Murphy
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: G R Scott
authors.initials: GR
authors.lastname: Budinger
authors.affiliation: Pulmonary and Critical Care Section, Department of Medicine, University of Chicago, Chicago, IL, United States of America.
authors.forename: Gökhan M
authors.initials: GM
authors.lastname: Mutlu
authors.affiliation: United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America; Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D004646:Emphysema / Q000139:chemically induced / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*
chemical_list: D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester