2-2--(hydroxynitrosohydrazono)bis-ethanamine and sodium-bisulfide

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.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenylyl Cyclases; Cells, Cultured; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glyburide; Humans; Hydrogen Sulfide; KATP Channels; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidase 1; NADPH Oxidases; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroso Compounds; Potassium Channel Blockers; rac1 GTP-Binding Protein; Signal Transduction; Sulfides; Superoxides; Time Factors