Abstract
The gaseous mediators hydrogen sulphide (H
2S) and nitric oxide (
NO) are synthesised in the body from
l-cysteine and
l-arginine, respectively. In the cardiovascular system,
NO is an important regulator of vascular tone and its over- or under-production has been linked to a variety of diseases. The physiological significance of H
2S is not yet clear but, like
NO, it exhibits vasodilator activity and may play a part in septic and haemorrhagic shock, hypertension, regulation of cardiac contractility, and in inflammation. To date, there have been no reports of a chemical interaction between H
2S and
NO. Here we show that incubation of the H
2S donor, sodium hydrosulphide, with a range of
NO donors and
NO gas in vitro leads to the formation of a nitrosothiol molecule as determined by a combination of techniques; electron paramagnetic resonance, amperometry, and measurement of nitrite. We further show that this nitrosothiol did not induce cGMP accumulation in cultured RAW264.7 cells unless
NO was released with Cu
2+. Finally, using liver homogenates from LPS treated rats we present evidence for the endogenous formation of this nitrosothiol. These findings provide the first evidence for the formation of a novel nitrosothiol generated by reaction between H
2S and
NO. We propose that generation of this nitrosothiol in the body may regulate the physiological effects of both
NO and H
2S.