Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification.
Basic Res Cardiol
; 106(4): 539-49, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21298436
ABSTRACT
In isolated cells, soluble guanylyl cyclase (sGC) activity is regulated by exogenous nitric oxide (NO) via downregulation of expression and posttranslational S-nitrosylation. The aim of this study was to investigate whether such regulatory mechanism impact on endothelium-dependent vasodilation in a newly developed mouse strain carrying an endothelial-specific overexpression of eNOS (eNOS(++)). When compared with transgene negative controls (eNOS(n)), eNOS(++)-mice showed a 3.3-fold higher endothelial-specific aortic eNOS expression, increased vascular cGMP and VASP phosphorylation, a L-nitroarginine (L-NA)-inhibitable decrease in systolic blood pressure, but normal levels of peroxynitrite and nitrotyrosine formation, endothelium-dependent aortic vasodilation and vasodilation to NO donors. Western blot analysis for sGC showed similar protein levels of sGC-α1 and sGC-ß1 subunits in eNOS(n) and eNOS(++). In striking contrast, the activity of isolated sGC was strongly decreased in lungs of eNOS(++). Semiquantitative evaluation of sGC-ß1-S-nitrosylation demonstrated that this loss of sGC activity is associated with increased nitrosylation of the enzyme in eNOS(++), a difference that disappeared after L-NA-treatment. Our data suggest the existence of a physiologic NO-dependent posttranslational regulation of vascular sGC in mammals involving S-nitrosylation as a key mechanism. Because this mechanism can compensate for reduction in vascular NO bioavailability, it may mask the development of endothelial dysfunction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Processamento de Proteína Pós-Traducional
/
Óxido Nítrico Sintase Tipo III
/
Guanilato Ciclase
Limite:
Animals
Idioma:
En
Revista:
Basic Res Cardiol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha