Adventitia-derived nitric oxide in rat aortas exposed to endotoxin: cell origin and functional consequences.
The role of adventitial cells in bacterial lipopolysaccharide (LPS)-induced vascular nitric oxide (NO) overproduction has been largely ignored. In rat aortas exposed to LPS in vitro or in vivo, it was found that adventitia contained the major part of NO synthase (NOS)-2 protein (Western blot and immunohistochemistry) and generated the largest amount of NO (electron paramagnetic resonance spin trapping). NOS-2 immunoreactive cells were mainly resident macrophages at an early stage (5 h, in vitro or in vivo) and fibroblasts at a later stage (20 h, in vitro). Adventitial NOS-2 activity largely accounted for 1) the relaxing effect of L-arginine in rings exposed to LPS in vivo, 2) generation of an "NO store" revealed by N-acetylcysteine-induced relaxation, and 3) formation of protein-bound dinitrosyl iron complexes in the medial layer of aortic rings exposed to LPS in vitro. In conclusion, the adventitia is a powerful source of NO triggered by LPS in the rat aorta. This novel source of NO has an important impact on smooth muscle function and might be implicated in various inflammatory diseases.
Kleschyov
A L
AL
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Unité Mixte de Recherche 7034, Centre National de la Recherche Scientifique, Université Louis Pasteur de Strasbourg, 67401 Illkirch, France. akleschyov@hotmail.com
Muller
B
B
Keravis
T
T
Stoeckel
M E
ME
Stoclet
J C
JC
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat