Kiss Levente, Deitch Edwin A, Szabó Csaba
Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, NJ 07103-2714, USA.
Life Sci. 2008 Oct 24;83(17-18):589-94. doi: 10.1016/j.lfs.2008.08.006. Epub 2008 Aug 28.
Hydrogen sulfide (H(2)S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H(2)S on vascular tone.
We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H(2)S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues.
We have found that in rat aortic rings: (1) H(2)S decreases ATP levels; (2) relaxations to H(2)S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H(2)S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP)-nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of K(ATP) channels is limited, while Cl(-)/HCO(3)(-) channels have a role in the relaxations. (6): We have observed that high concentrations of H(2)S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree.
H(2)S, a new gasotransmitter of emerging importance, leads to relaxation via Cl(-)/HCO(3)(-) channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue.
低浓度硫化氢（H₂S）作为一种生理性内源性血管舒张分子，而高浓度时可引发细胞毒性作用。我们研究的目的是阐明H₂S对血管张力产生影响的潜在机制。
我们在预收缩的大鼠胸主动脉环中体外测量血管张力，并测试了不同氧水平以及多种影响已知血管舒张途径的抑制剂的作用。我们还比较了高浓度H₂S与氧化磷酸化药理抑制剂的血管效应。此外，我们测量了相同血管组织中的三磷酸腺苷（ATP）水平。
我们发现，在大鼠主动脉环中：（1）H₂S降低ATP水平；（2）对H₂S的舒张作用取决于环境氧浓度；（3）前列腺素不参与H₂S诱导的舒张；（4）3',5'-环磷酸鸟苷（cGMP）-一氧化氮（NO）途径在舒张中不起作用；（5）ATP敏感性钾通道的作用有限，而Cl⁻/HCO₃⁻通道在舒张中起作用。（6）：我们观察到，高浓度H₂S以类似于氰化钠的方式舒张主动脉环，并且两种试剂将细胞ATP水平降低到相当程度。
H₂S是一种新出现且具有重要意义的气体信号分子，通过Cl⁻/HCO₃⁻通道和代谢抑制导致舒张，并且这两个因素的相互作用取决于组织的氧水平。
