Exogenous Hydrogen Sulfide Inhibits Superoxide Formation, NOX-1 Expression and Rac₁ Activity in Human Vascular Smooth Muscle Cells

Abstract

The activity of NADPH oxidase (NOX) is blocked by nitric oxide (NO). Hydrogen sulfide (H₂S) is also produced by blood vessels. It is reasonable to suggest that H₂S may have similar actions to NO on NOX. In order to test this hypothesis, the effect of sodium hydrosulfide (NaHS) on O₂^– formation, the expression of NOX-1 (a catalytic subunit of NOX) and Rac₁ activity (essential for full NOX activity) in isolated vascular smooth muscle cells (hVSMCs) was investigated. hVSMCs were incubated with the thromboxane A₂ analogue U46619 ± NaHS for 1 or 16 h, and O₂^– formation, NOX-1 expression and Rac₁ activity were assessed. The possible interaction between H₂S 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 O₂^– formation following incubation of 1 h (IC₅₀, 30 nM) and 16 h (IC₅₀, 20 nM), blocked NOX-1 expression and inhibited Rac₁ activity. These inhibitory effects of NaHS were mediated by the cAMP-protein-kinase-A axis. Exogenous H₂S prevents NOX-driven intravascular oxidative stress through an a priori inhibition of Rac₁ and downregulation of NOX-1 protein expression, an effect mediated by activation of the adenylylcyclase-cAMP-protein-kinase-G system by H₂S.

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

“…12 On the basis of these findings, it can be proposed that the increased superoxide dismutase activity would scavenge the superoxide anions in the vessel walls thereby increasing the bioavailability of NO causing preglomerular arteriolar vasodilatation. However, superoxide anions levels were not measured in the present study so the possibility of direct inhibition of superoxide by NaHS 36 or tempol 37 cannot be ruled out. The increase in creatinine clearance and renal cortical blood perfusion support the view that the combination of NaHS and tempol led to an interaction that resulted in a renal arteriolar vasodilatation and reduced pre-glomerular arteriolar resistance.…”

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

“…Inhibition of 'oxidative stress' by inactivating enzymes or the direct 'scavenging' of the oxidant species would be expected to contribute to the many potential anti-inflammatory effects of H 2 S. In vitro experiments have shown that H 2 S generated from sulfide salts (Na 2 S and NaSH) inhibits cellular damage and intracellular protein oxidation induced by HOCl [77,78], ONOO - [79] and • NO [34,80]. NaSH is also reported to scavenge and/or degrade lipid peroxides [81,82] and inhibit the expression and activity of NAD(P)H oxidase [83,84]. Increased hepatic glutathione (GSH) synthesis and decreased lipid peroxidation are also observed with Na 2 S treatment in a murine hepatic ischemia-reperfusion injury model [85].…”

The Effect of Hydrogen Sulfide Donors on Lipopolysaccharide-Induced Formation of Inflammatory Mediators in Macrophages

“…In addition, H 2 S ''scavenges'' proinflammatory oxidants such nitric oxide ( NO), peroxynitrite (ONOO -), hypochlorous acid (HOCl) (25,26), superoxide, and hydrogen peroxide (3,6,15); such effects might be expected to alleviate inflammation. Finally, S-diclofenac (an H 2 S-releasing derivative of the nonsteroidal antiinflammatory drug, diclofenac) exhibits more-pronounced antiinflammatory activity in endotoxic shock (11) and against carrageenan-induced hindpaw edema (18) in the rat than does diclofenac.…”