Tc. Carpenter et Kr. Stenmark, Hypoxia decreases lung neprilysin expression and increases pulmonary vascular leak, AM J P-LUNG, 281(4), 2001, pp. L941-L948
Citations number
19
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Although prior studies suggest that hypoxia may increase pulmonary vascular
permeability, the mechanisms responsible for that effect remain uncertain.
Neprilysin (neutral endopeptidase) is a cell surface metallopeptidase that
degrades several vasoactive peptides including substance P and bradykinin.
We hypothesized that hypoxia could reduce lung neprilysin expression, lead
ing to increased vascular leak. Weanling rats were exposed to normobaric hy
poxia (inspired O-2 fraction = 0.1). Lung neprilysin activity was significa
ntly decreased after 24 and 48 h of hypoxia (P<0.006). The decrease in enzy
me activity was associated with decreased lung neprilysin protein content a
nd decreased lung neprilysin mRNA expression. Immunohistochemistry showed a
predominantly perivascular distribution of neprilysin, with dear reduction
s in neprilysin immunoreactivity after exposure to hypoxia. Exposure to hyp
oxia for 24 h also caused marked increases in vascular leak (P=0.008), whic
h were reversed by the administration of recombinant neprilysin. The hypoxi
a-induced increase in leak was also reversed by substance P and bradykinin
receptor antagonists. We conclude that in young rats hypoxia decreases lung
neprilysin expression, which contributes to increased pulmonary vascular l
eak via substance P and bradykinin receptors.