Exogenous Hydrogen Sulfide Inhibits Superoxide Formation, NOX-1 Expression and Rac(1) Activity in Human Vascular Smooth Muscle Cells

S Muzaffar, N Shukla, M Bond, AC Newby, G Angelini, A Sparatore, P Del Soldato, JY Jeremy

Research output: Contribution to journalArticle (Academic Journal)peer-review

96 Citations (Scopus)

Abstract

The activity of NADPH oxidase (NOX) is blocked by nitric oxide (NO). Hydrogen sulfide (H(2)S) is also produced by blood vessels. It is reasonable to suggest that H(2)S may have similar actions to NO on NOX. In order to test this hypothesis, the effect of sodium hydrosulfide (NaHS) on O(2)(-) formation, the expression of NOX-1 (a catalytic subunit of NOX) and Rac(1) activity (essential for full NOX activity) in isolated vascular smooth muscle cells (hVSMCs) was investigated. hVSMCs were incubated with the thromboxane A(2) analogue U46619 +/- NaHS for 1 or 16 h, and O(2)(-) formation, NOX-1 expression and Rac(1) activity were assessed. The possible interaction between H(2)S and NO was also studied by using an NO synthase inhibitor, L-NAME, and an NO donor, DETA-NONOate. The role of K(ATP) channels was studied by using glibenclamide. NaHS inhibited O(2)(-) formation following incubation of 1 h (IC(50), 30 nM) and 16 h (IC(50), 20 nM), blocked NOX-1 expression and inhibited Rac(1) activity. These inhibitory effects of NaHS were mediated by the cAMP-protein-kinase-A axis. Exogenous H(2)S prevents NOX-driven intravascular oxidative stress through an a priori inhibition of Rac(1) and downregulation of NOX-1 protein expression, an effect mediated by activation of the adenylylcyclase-cAMP-protein-kinase-G system by H(2)S. Copyright © 2008 S. Karger AG, Basel.
Translated title of the contributionExogenous Hydrogen Sulfide Inhibits Superoxide Formation, NOX-1 Expression and Rac(1) Activity in Human Vascular Smooth Muscle Cells
Original languageEnglish
Pages (from-to)521 - 528
Number of pages8
JournalJournal of Vascular Research
Volume7;45(6)
Publication statusPublished - May 2008

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