Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function.

Published

Journal Article

Although protein S-nitrosylation is increasingly recognized as mediating nitric oxide (NO) signaling, roles for protein denitrosylation in physiology remain unknown. Here, we show that S-nitrosoglutathione reductase (GSNOR), an enzyme that governs levels of S-nitrosylation by promoting protein denitrosylation, regulates both peripheral vascular tone and β-adrenergic agonist-stimulated cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR-deficient mice exhibited reduced peripheral vascular tone and depressed β-adrenergic inotropic responses that were associated with impaired β-agonist-induced denitrosylation of cardiac ryanodine receptor 2 (RyR2), resulting in calcium leak. These results indicate that systemic hemodynamic responses (vascular tone and cardiac contractility), both under basal conditions and after adrenergic activation, are regulated through concerted actions of NO synthase/GSNOR and that aberrant denitrosylation impairs cardiovascular function. Our findings support the notion that dynamic S-nitrosylation/denitrosylation reactions are essential in cardiovascular regulation.

Full Text

Duke Authors

Cited Authors

  • Beigi, F; Gonzalez, DR; Minhas, KM; Sun, Q-A; Foster, MW; Khan, SA; Treuer, AV; Dulce, RA; Harrison, RW; Saraiva, RM; Premer, C; Schulman, IH; Stamler, JS; Hare, JM

Published Date

  • March 2012

Published In

Volume / Issue

  • 109 / 11

Start / End Page

  • 4314 - 4319

PubMed ID

  • 22366318

Pubmed Central ID

  • 22366318

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1113319109

Language

  • eng