L‐Cysteine and Sodium Hydrosulphide Inhibit Spontaneous Contractility in Isolated Pregnant Rat Uterine Strips in vitro

Abstract

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (nΩ22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10 ª8 -10 ª3 M of L-cysteine (nΩ8) or sodium hydrosulphide (nΩ8) were subsequently applied to the tissue. In a third series of experiments (nΩ6) the effect of doses of 10 ª9 , 10 ª6 and 10 ª3 M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dosedependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10 ª3 M. This study has demonstrated novel tocolytic actions of Lcysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.

Hydrogen sulfide mediates vasoactivity in an O2-dependent manner

“…In addition, serum H 2 S levels are elevated during septic or endotoxic shock (23), perhaps contributing to the associated drop in blood pressure. Rings or strips of vascular smooth muscle or uterine smooth muscle exposed to NaHS exhibit a decrease in tension, with an IC 50 of 125-150 M for aorta under air-saturated conditions of ϳ200 M O 2 (22,41,55). Whereas the data support a role for H 2 S in modulating vascular function, it is unlikely that these H 2 S levels occur in vivo.…”

The vasorelaxant effect of hydrogen sulfide is enhanced in streptozotocin-induced diabetic rats

“…Endothelium is not involved in the vasorelaxant effect of H 2 S, whereas ATP-sensitive potassium channels are responsible for the H 2 S-induced relaxation in vascular smooth muscle (Hosoki et al 1997;Zhao et al 2001). The mechanism of the relaxation response in nonvascular smooth muscles, i.e., guinea-pig ileum and rat uterine, has not been identified yet (Sidhu et al 2001;Teague et al 2002).…”

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

“…Products of this H2S/NO interaction appear to have pronounced biological effects; however the nature of the reaction intermediates is currently unclear and many inconsistencies remain; for example, H2S donors were found to either potentiate or attenuate relaxation effect of NO donors in isolated aortic rings in vitro [15,16], or result in complete loss of vasodepressor activity in anesthetized rats [16]. H2S was shown to relax uterus from pregnant [17,18] and non-pregnant rats [19], and sodium nitroprusside (SNP) prevented H2S induced relaxation of rat uterus [20]. Thionitrous acid (HSNO) has been proposed to represent an important carrier of bioactivity of the interaction of S-nitrosothiols with H2S [10], but the evidence provided appears to be inconsistent with the known chemical properties of HSNO.…”