Ali M Y, Ping C Y, Mok Y-Yp, Ling L, Whiteman M, Bhatia M, Moore P K
Department of Pharmacology, Cardiovascular Biology Research Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Br J Pharmacol. 2006 Nov;149(6):625-34. doi: 10.1038/sj.bjp.0706906. Epub 2006 Oct 3.
The aim of these experiments was to evaluate the significance of the chemical reaction between hydrogen sulphide (H2S) and nitric oxide (NO) for the control of vascular tone.
The effect of sodium hydrosulphide (NaHS; H2S donor) and a range of NO donors, such as sodium nitroprusside (SNP), either alone or together, was determined using phenylephrine (PE)-precontracted rat aortic rings and on the blood pressure of anaesthetised rats.
Mixing NaHS with NO donors inhibited the vasorelaxant effect of NO both in vitro and in vivo. Low concentrations of NaHS or H2S gas in solution reversed the relaxant effect of acetylcholine (ACh, 400 nM) and histamine (100 microM) but not isoprenaline (400 nM). The effect of NaHS on the ACh response was antagonized by CuSO(4) (200 nM) but was unaffected by glibenclamide (10 microM). In contrast, high concentrations of NaHS (200-1600 microM) relaxed aortic rings directly, an effect reduced by glibenclamide but unaffected by CuSO4. Intravenous infusion of a low concentration of NaHS (10 micromol kg(-1) min(-1)) into the anaesthetized rat significantly increased mean arterial blood pressure. L-NAME (25 mg kg(-1), i.v.) pretreatment reduced this effect.
These results suggest that H2S and NO react together to form a molecule (possibly a nitrosothiol) which exhibits little or no vasorelaxant activity either in vitro or in vivo. We propose that a crucial, and hitherto unappreciated, role of H2S in the vascular system is the regulation of the availability of NO.
这些实验的目的是评估硫化氢（H₂S）与一氧化氮（NO）之间的化学反应对血管张力控制的意义。
使用苯肾上腺素（PE）预收缩的大鼠主动脉环以及麻醉大鼠的血压，测定硫氢化钠（NaHS；H₂S供体）和一系列NO供体（如硝普钠（SNP））单独或共同作用的效果。
将NaHS与NO供体混合在体外和体内均抑制了NO的血管舒张作用。溶液中低浓度的NaHS或H₂S气体可逆转乙酰胆碱（ACh，400 nM）和组胺（100 μM）的舒张作用，但对异丙肾上腺素（400 nM）无此作用。NaHS对ACh反应的影响可被硫酸铜（200 nM）拮抗，但不受格列本脲（10 μM）影响。相反，高浓度的NaHS（200 - 1600 μM）可直接使主动脉环舒张，该作用可被格列本脲减弱，但不受硫酸铜影响。向麻醉大鼠静脉输注低浓度的NaHS（10 μmol kg⁻¹ min⁻¹）可显著提高平均动脉血压。L - NAME（25 mg kg⁻¹，静脉注射）预处理可降低此效应。
这些结果表明，H₂S与NO共同反应形成一种分子（可能是亚硝基硫醇），其在体外或体内几乎不表现出血管舒张活性。我们提出，H₂S在血管系统中一个关键且迄今未被重视的作用是调节NO的可用性。
