Nitric oxide prevents alveolar senescence and emphysema in a mouse model

PloS One
Amanda E BoeDouglas E Vaughan

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.

References

Dec 6, 2000·The Journal of Clinical Investigation·Y KasaharaN F Voelkel
Aug 25, 2001·American Journal of Respiratory and Critical Care Medicine·J A BarberàR Rodriguez-Roisin
May 10, 2002·Nucleic Acids Research·Richard M Cawthon
May 11, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shari M LeuwerkeVictor E Laubach
Jun 11, 2002·Journal of Molecular and Cellular Cardiology·Koichi KaikitaDouglas E Vaughan
Jun 23, 2004·Journal of Applied Physiology·Kechun TangEllen C Breen
Aug 5, 2006·American Journal of Respiratory and Critical Care Medicine·Takao TsujiAtsushi Nagai
Feb 5, 2008·The Journal of Clinical Investigation·Laimute Taraseviciene-Stewart, Norbert F Voelkel
Apr 7, 2009·American Journal of Respiratory Cell and Molecular Biology·Jeroen A J VanoirbeekWim Janssens
Aug 18, 2009·Respiratory Research·Elisabet FerrerJoan Albert Barberà
Aug 17, 2010·American Journal of Respiratory and Critical Care Medicine·Joanne L WrightAndrew M Churg
Jun 1, 2011·Pulmonary Pharmacology & Therapeutics·Samuel Santos ValençaLuís Cristóvão Porto
Sep 25, 2012·Free Radical Biology & Medicine·Manuella LanzettiSamuel Santos Valença
Jan 3, 2013·The Journal of Clinical Investigation·Saptarsi M Haldar, Jonathan S Stamler

❮ Previous
Next ❯

Citations

Jun 3, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Douglas E VaughanAsish K Ghosh
Dec 7, 2018·Biological & Pharmaceutical Bulletin·Kunihiro SonodaJun Kobayashi
Dec 1, 2020·Journal of Biomolecular Structure & Dynamics·Jan Mohammad Mir, Ram Charitra Maurya

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

Scireq
FlexiVent
Take
ImagePro
TissueGnostics

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.