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

Dechun Li, Victor E. Laubach, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia upregulates endothelial (e) nitric oxide synthase (NOS), but how eNOS affects soluble guanylate cyclase (sGC) protein expression in hypoxia-induced pulmonary hypertension is unknown. Wild-type (WT), eNOS-deficient [eNOS(-/-)], and inducible NOS (iNOS)-deficient [iNOS(-/ -)] mice were used to investigate the effects of lack of NO from different NOS isoforms on sGC activity and protein expression and its relationship to the muscularization of the pulmonary vasculature. After 6 days of hypoxic exposure (10% O2), the 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 vascular muscularization were determined, and protein analysis for eNOS, iNOS, and sGC was performed. Results demonstrated that there were significant increases of RV/LV+S in all animals treated with hypoxia. In hypoxic WT and iNOS(-/-) mice, eNOS and sGC α1- and β1-protein increased twofold; cGMP levels and the number of muscularized vessels also increased compared with hypoxic eNOS(-/-) mice. There was a twofold increase of iNOS protein in WT and eNOS(-/-) mice, and the basal iNOS protein concentration was higher in eNOS(-/-) mice than in WT mice. In contrast, the eNOS(-/-) mouse lung showed no eNOS protein expression, lower cGMP concentrations, and no change of sGC protein levels after hypoxic exposure compared with its normoxic 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 vasculature.

Original languageEnglish (US)
Pages (from-to)L369-L376
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number2 25-2
DOIs
StatePublished - 2001

Keywords

  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Pulmonary hypertension
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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