Upregulation of lung soluble guanylate cyclase during chronic hypoxia is prevented by deletion of eNOS

Citation
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
ISSN journal
1040-0605 → ACNP
Volume
281
Issue
2
Year of publication
2001
Pages
L369 - L376
Database
ISI
SICI code
1040-0605(200108)281:2<L369:UOLSGC>2.0.ZU;2-B
Abstract
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.