Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice.

Abstract:

:Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease. In chimeric mice lacking iNOS in bone marrow (BM)-derived cells, PH was dependent on iNOS from BM-derived cells, whereas emphysema development was dependent on iNOS from non-BM-derived cells. Similar regulatory and structural alterations as seen in mouse lungs were found in lung tissue from humans with end-stage COPD.

journal_name

Cell

journal_title

Cell

authors

Seimetz M,Parajuli N,Pichl A,Veit F,Kwapiszewska G,Weisel FC,Milger K,Egemnazarov B,Turowska A,Fuchs B,Nikam S,Roth M,Sydykov A,Medebach T,Klepetko W,Jaksch P,Dumitrascu R,Garn H,Voswinckel R,Kostin S,Seeger W,S

doi

10.1016/j.cell.2011.08.035

subject

Has Abstract

pub_date

2011-10-14 00:00:00

pages

293-305

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(11)01005-1

journal_volume

147

pub_type

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