Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?
Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?
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DOI：
10.1038/sj.bjp.0706906
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发表时间：
2006-11-01
影响因子：
7.3
通讯作者：
Moore, P. K.
中科院分区：
文献类型：
--
作者：
Ali, M. Y.;Ping, C. Y.;Moore, P. K.
背景和目的：这些实验的目的是评估硫化氢（H2S）和一氧化氮（NO）之间的化学反应对于控制血管张力的意义。实验方法：硫氢化钠的作用（NaHS; H2S供体）和一系列NO供体，例如硝普钠（SNP），单独或一起，测定使用phenyllephaline（PE）预收缩大鼠主动脉环和麻醉rates.Key结果：混合NaHS与NO供体抑制血管舒张作用的NO在体外和体内的血压。溶液中低浓度的NaHS或H2S气体逆转了乙酰胆碱（ACh，400 nM）和组胺（100 μ M）的松弛作用，但不逆转异丙肾上腺素（400 nM）。NaHS对ACh反应的影响被CuSO 4（200 nM）拮抗，但不受格列本脲（10 μ M）的影响。相比之下，高浓度的NaHS（200-1600 μ M）直接放松主动脉环，格列本脲降低了这种作用，但不受CuSO 4的影响。麻醉大鼠静脉输注低浓度NaHS（10 μ mol kg（-1）min（-1））可显著增加平均动脉血压。L-NAME（25 mg/kg，i.v.）结论和意义：这些结果表明，H2S和NO反应在一起，形成一个分子（可能是亚硝基硫醇），表现出很少或没有血管舒张活性，无论是在体外或体内。我们提出，一个至关重要的，迄今为止未得到赞赏的，在血管系统中的作用是H2S的NO的可用性的调节。
Background and Purpose: 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.Experimental Approach: 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.Key Results: 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 mu M) but not isoprenaline (400 nM). The effect of NaHS on the ACh response was antagonized by CuSO4 (200 nM) but was unaffected by glibenclamide (10 mu M). In contrast, high concentrations of NaHS (200-1600 mu M) relaxed aortic rings directly, an effect reduced by glibenclamide but unaffected by CuSO4. Intravenous infusion of a low concentration of NaHS (10 mu mol 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.Conclusions and Implications: 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.