Dc. Li et al., Upregulation of lung soluble guanylate cyclase during chronic hypoxia is prevented by deletion of eNOS, AM J P-LUNG, 281(2), 2001, pp. L369-L376
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Hypoxia upregulates endothelial (e) nitric oxide synthase (NOS), but how eN
OS affects soluble guanylate cyclase (sGC) protein expression in hypoxia-in
duced pulmonary hypertension is unknown. Wild-type (WT), eNOS-deficient [eN
OS( -/-)], and inducible NOS (iNOS)-deficient [iNOS(-/-)] mice were used to
investigate the effects of lack of NO from different NOS isoforms on sGC a
ctivity and protein expression and its relationship to the muscularization
of the pulmonary vasculature. After 6 days of hypoxic exposure (10% O-2), t
he ratios of the right ventricle to left ventricle + septum weight (RV/LV+S
) and right ventricle weight to body weight, the lung sGC activity, and vas
cular muscularization were determined, and protein analysis for eNOS, iNOS,
and sGC was performed. Results demonstrated that there were significant in
creases of RV/LV+S in all animals treated with hypoxia. In hypoxic WT and i
NOS(-/-) mice, eNOS and sGC alpha (1)- and beta (1)-protein increased twofo
ld; cGMP levels and the number of muscularized vessels also increased compa
red with hypoxic eNOS(-/-) mice. There was a twofold increase of iNOS prote
in in WT and eNOS(-/-) mice, and the basal iNOS protein concentration was h
igher in eNOS(-/-) mice than in WT mice. In contrast, the eNOS(-/-) mouse l
ung showed no eNOS protein expression, lower cGMP concentrations, and no ch
ange of sGC protein levels after hypoxic exposure compared with its normoxi
c controls (P > 0.34). These results suggest that eNOS, but not iNOS, is a
major regulator of sGC activity and protein expression in the pulmonary vas
culature.