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01-07-2011 | Original Contribution

Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification

Authors: Marc Oppermann, Tatsiana Suvorava, Till Freudenberger, Vu Thao-Vi Dao, Jens W. Fischer, Martina Weber, Georg Kojda

Published in: Basic Research in Cardiology | Issue 4/2011

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 (eNOSⁿ), 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-β1 subunits in eNOSⁿ and eNOS⁺⁺. In striking contrast, the activity of isolated sGC was strongly decreased in lungs of eNOS⁺⁺. Semiquantitative evaluation of sGC-β1-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.

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Title: Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification
Authors: Marc Oppermann
Tatsiana Suvorava
Till Freudenberger
Vu Thao-Vi Dao
Jens W. Fischer
Martina Weber
Georg Kojda
Publication date: 01-07-2011
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 4/2011
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-011-0160-5

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