P80: Hydrogen sulphide impairs bioactivity of nitric oxide by superoxide-dependent and -independent mechanisms

Abstract

Nitric oxide (NO) und hydrogen sulfide (H2S) are gaseous transmitters that regulate many physiological processes. In the vascular system, both molecules promote vasodilation suggesting that H2S may act in a synergy with NO. However, when measuring NO-induced cGMP formation in endothelial cells we observed that coincubation of the cells with the H2S donor sodium hydrogen sulfide (NaHS) markedly diminished the NO response. Similarly, incubation of NO with NaHS in buffered solution led to a rapid decline in the NO concentration measured by an NO chemiluminescence analyzer. The effect was less pronounced in the presence of superoxide dismutase (SOD), demonstrating that part of the NO was inactivated by superoxide arising from the autoxidation of H2S according to the following equations: H2S↔HS-+H+ HS-+M(n+1)+→HS+Mn+ Mn++O2→M(n+1)++O2- O2-+NO→ONOO- Inactivation of NO in the presence of SOD was accompanied by transient formation thionitrous acid and accumulation of nitrite. The reaction was enhanced upon increasing the pH from 7.4 to 9.0 and abolished at pH 6.0, suggesting HS− rather than H2S as reactant. Based on the data we hypothesize that NO directly interacts with HS− to thionitrous acid, which decomposes to nitrite. NO+O2+HS-→HSNO+O2- HSNO+H2O→H2S+NO2-+H+ In summary, our data demonstrate that H2S reduced the bioactivity of NO by two distinct reactions involving direct interaction of NO with HS− as well as O2--induced inactivation of NO.