Hydrogen sulfide (H2S) is involved in blood pressure regulation. We evaluated hemodynamic effects of Na2S and morpholin-4-ium (4-methoxyphenyl)(morpholino)phosphinodithioate (GYY4137), H2S donors. GYY4137 is the most widely studied slow-releasing H2S donor, however, its ability to release H2S under physiological conditions is unclear. Hemodynamics were recorded in anaesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% dimethyl sulfoxide), GYY4137 or Na2S. The stability of GYY4137 in buffers and in plasma was evaluated with nuclear magnetic resonance. The vehicle, as well as GYY4137, given IV did not affect mean arterial blood pressure (MABP), whereas Na2S produced a significant decrease in MABP. Similarly, IP given Na2S, but not GYY4137, lowered MABP. In the buffers at pH of 7.4 and 5.5 and in rat plasma no reaction of GYY4137 was found during 18 hours of observation. In contrast, rapid decomposition of GYY4137 occurred in buffers at pH 2.0. In conclusion, parenteral GYY4137 does not exert a hemodynamic effect in Wistar-Kyoto rats. This seems to be due to the high stability of GYY4137 at physiological pH. Therefore, it is likely that widely reported biological effects of GYY4137 are not H2S-dependent but may depend on GYY4137 itself. However, the H2S-dependent biological effects of GYY4137 may be expected in tissues characterized by low pH.
Hydrogen sulfide (H2S) is endogenously synthesized from l-cysteine in reactions catalyzed by cystathionine beta-synthase (CBS, EC 4.2.1.22) and gamma-cystathionase (CSE, EC 4.4.1.1). The role of 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) in H2S generation is also considered; it could be important for tissues with low CTH activity, e.g. cells of the nervous system. The expression and activity of CBS, CTH, and MPST were detected in the human glioblastoma-astrocytoma (U-87 MG) and neuroblastoma (SHSY5Y) cell lines. In both cell lines, the expression and activity of MPST were the highest among the investigated enzymes, suggesting its possible role in the generation of H2S. The RP-HPLC method was used to determine the concentration of cystathionine and alpha-ketobutyrate, products of the CBS- and CTH-catalyzed reactions. The difference in cystathionine levels between cell homogenates treated with totally CTH-inhibiting concentrations of dl-propargylglycine and without the inhibitor was used to evaluate the activity of CBS. The higher expression and activity of CBS, CTH and MPST in the neuroblastoma cells were associated with more intensive generation of H2S in the presence of 2 mM cysteine. A threefold higher level of sulfane sulfur, a potential source of hydrogen sulfide, was detected in the astrocytoma cells in comparison to the neuroblastoma cells.
Hydrogen sulfide is a simple, non organic chemical compound with the general formula of H2S. It has very characteristic odour similar to rotten eggs. H2S is heavier than air and it has very good dissolution in water (it occurs in the form of ions). Hydrogen sulfide takes part in a lot of important functions and has a positive impact on many systems like the excretory, nervous and circulatory system. Studies have shown that the role of hydrogen sulphide in the cardiovascular system is vast and complex. This compound is involved in many essential processes for our body associated with angiogenesis, blood clotting action and blood platelet activation. It has been investigated that H2S takes part in the protection against atherosclerosis.
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Siarkowodór to prosty, nieorganiczny związek chemiczny o ogólnym wzorze H2S. Jego cechą charakterystyczną jest zapach – przypomina on aromat zgniłego jajka. Jest to związek cięższy niż powietrze, bardzo dobrze rozpuszczalny w wodzie (występuje w niej w postaci jonów). Siarkowodór spełnia wiele bardzo ważnych funkcji w organizmie człowieka i ma pozytywny wpływ na wiele układów – między innymi na układ wydalniczy, nerwowy czy układ krążenia. Badania dowiodły, iż rola siarkowodoru w układzie krążenia jest różnorodna. Związek ten uczestniczy w wielu istotnych dla naszego organizmu procesach związanych z angiogenezą, krzepnięciem krwi czy aktywacją płytek krwi oraz chroni przed miażdżycą.
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