Effects of nitric oxide and hydrogen sulfide on the relaxation of pulmonary arteries in rats

Background The balance between vasodilation and vasoconstriction plays a major role in maintaining vascular homeostasis. However, the underlying mechanisms are unclear. More and more evidence suggested that there was an interaction in the regulation of vasorelaxation between nitric oxide （NO） and hydrogen sulfide （H2S）. We explored the interaction between and effects of NO and H2S on the relaxation of pulmonary arteries in rats. Methods Seven male Sprague-Dawley rats were anaesthetized with chloral hydrate and the pulmonary arteries of each rat separated for the study of vascular activities. The vasorelaxing activities of pulmonary artery rings in response to different doses of a NO donor, sodium nitroprusside （SNP）, or a H2S donor, sodium hydrogensulfide （NariS）, were measured in vitro. When pulmonary artery rings were treated with a cystathionine-y-lyase inhibitor, DL-propargylglycine, in the presence of SNP or a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester, in the presence of NariS, the changes in relaxing activities were analyzed. Results The relaxation of pulmonary artery rings was in a dose dependent manner in response to either SNP or NariS. The relaxation rates of pulmonary artery rings increased from （30.90±4.62） % to （60.50±8.08） % when the concentration of SNP increased from 1 pmol/L to 3 pmol/L and from （26.13±4.12） % to （53.09±14.01） % when the concentration of NariS increased from 25 pmol/L to 100 μmol/L. However, when appropriate inhibitor was added, the relaxation responses to SNP and NariS decreased. Conclusions The results suggested that similarly to NO, H2S acted as a vasorelaxant either independently of, or synergistically with NO in the regulation of vasorelaxation. The interaction between NO and H2S played an important role in regulating relaxing activities of pulmonary arteries.     

Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats

Background  Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation.

Methods  Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na⁺-K⁺-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student’s t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes.

Results   Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta-mercaptopyruvate also increased mean arterial pressure (P <0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P <0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P <0.01). Glibenclamide (a K_ATP channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P <0.01) after treatment with L-cysteine, association with decreasing Na⁺-K⁺-ATPase activity in cardiac or aortic sarcolemmal vesicles (P <0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na⁺-K⁺-ATPase activity in cardiac and aortic sarcolemmal vesicles.

Conclusion  Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.

     

硫化氢对家兔肠系膜动脉血管环张力调节研究

目的:观察硫化氢(H2S)对家兔肠系膜血管环张力的调节作用,及其可能的作用机制。方法:应用离体血管环张力测定技术,用金属钩将3mm左右的动脉环悬置于含K-H液的离体器官浴槽中,观察硫化氢在血管环张力的作用,由计算机生物信号采集处理系统进行记录分析,检测血管环张力的变化,制作浓度反应曲线。结果:(1)外源性的NaHS(H2S的供体)可以剂量依赖性地舒张由氯化钾(KCL)预收缩的肠系膜动脉血管环。(2)用ATP敏感性钾通道(KA T P)通道阻断剂格列苯脲(Gli)、钙通道的开放剂1,4-二氢-2,6-二甲基-5-硝基-4-(2-[三氟甲基]苯基)吡啶-3-羧酸甲酯(Bay K8644)、NO合酶的抑制剂左旋硝基精氨酸甲酯(L-NAME)和环氧合酶阻断剂吲哚美辛预处理以及去除血管内皮后,H2S的舒张效应均被显著抑制,浓度反应曲线均明显右移。(3)给予鸟苷酸环化酶的抑制剂1H-(1,2,4)恶二唑(4,3-α)喹喔啉-1-酮(ODQ)预处理后,对H2S的舒张作用没有显著改变。结论:H2S在50～800μmol/L之间浓度依赖性的舒张家兔肠系膜动脉,部分是通过开放KA T P通道和关闭L型钙通道实现的,但与3ˊ,5ˊ-环一磷酸鸟苷(cGMP)途径无关。此作用是内皮依赖性的,且与一氧化氮(NO)和前列环素(PGI2)具有协同作用。     

内源性二氧化硫对心血管系统的调节意义

自上世纪80年代以来,已陆续证实代谢产生的内源性气体分子--一氧化氮(nitric oxide, NO)、一氧化碳(carbon monoxide, CO)和硫化氢(hydrogen sulfide, H2S)可以作为信号分子参与机体稳态调节,并且具有重要的生理和病理生理意义, 由此开创了"气体信号分子家系"的新领域.我们特别关注的是至今仍被认为是代谢废物的其他内源性气体分子的生物学调节作用,以期探寻气体信号分子家系的新成员.     

气体信号分子在心血管疾病发病中的意义

气体分子一氧化氮(NO)的发现开创了气体信号分子这一新型研究领域,目前已发现3种气体信号分子:NO、一氧化碳(CO)和硫化氢(H2S).他们在体内内源性生成,发挥广泛的生物学效应,本文仅就3种气体信号分子在心血管系统中的意义进行简要阐述.在心血管系统中内源性气体信号分子NO、CO和H2S分别与其相应的合成酶一氧化氮合酶(NOS)、血红素加氧酶(HO)和胱硫醚-γ-裂解酶(CSE)形成独立而又相互关联的体系(NO/NOS体系、CO/HO体系、H2S/CSE体系),不仅参与心血管系统生理状态下功能和结构的维持,而且在高血压、肺动脉高压、感染性休克、动脉粥样硬化等心血管疾病发病中发挥重要的病理生理学作用.     

硫化氢和同型半胱氨酸在动脉粥样硬化病变中的研究现状

动脉粥样硬化(atherosclerosis,AS)性病变是目前世界上心血管疾病的发生率与死亡率高的首位原因,严重危害人们的生命健康安全。动脉粥样硬化主要累及大中动脉,是一种慢性复杂的累进型病理过称。高同型半胱氨酸血症(Hyperho-mocysteinemia,HHcy)是动脉粥样硬化形成的独立危险因子,它可以通过转硫基作用等转化成硫化氢,但是其致病机制尚未完全阐明。近年来,硫化氢(hydrogen sulfide,H2S)因其在心血管健康和内稳态调节平衡方面的诸多积极性作用而受到重要关注。新近研究发现H2S在动脉粥样硬化病变过程中发挥重要作用。AS的发生发展与同型半胱氨酸(homocysteine,Hcy)和H2S存在一定的内在联系,本文拟对此方面的研究和认识作一综述。     

硫化氢在心血管疾病中的研究进展*

硫化氢被认为是重要的内源性气体递质,可以在哺乳动物的组织中合成并自由地穿过细胞膜,通过多种机制对心肌细胞发挥保护作用,并在心血管系统内发挥许多生物学效应。内源性硫化氢和外源性硫化氢供体,如硫氢化钠、硫化二钠、P-（4-甲氧基苯基）-p-4-吗啉代二硫代磷酸等的释放,在包括动脉粥样硬化、高血压、心肌损伤和心力衰竭等心血管疾病中发挥重要作用。然而,关于硫化氢在健康及疾病状态中的作用及机制仍待更深入地探讨。该文将对硫化氢在心血管疾病中的研究进展进行概述,并讨论其作用机制。     

高肺血流量对肺血管结构及胱硫醚-γ-裂解酶基因表达的影响

目的：探讨高肺血流量所致肺动脉高压大鼠肺血管结构和内源性硫化氢体系的变化。方法：SD大鼠共16只，随机分为分流组及对照组。对分流组大鼠行腹主动脉—下腔静脉分流术。11周后以右心导管法测定肺动脉平均压(pulmonary artery mean pressure，mPAP)。检测右心室／体重(right ventricle／body weight，RV／BW)和右心室／左心室 室间隔(right ventricle／left ventricle plus septum，RV／LV S)比值。并且以光学显微镜和电子显微镜观测肺血管结构的变化。以分光光度法测定血浆硫化氢(hydrogen sulfide，H2S)含量。化学法测定肺组织硫化氢产出率，以原位杂交的方法检测肺动脉胱硫醚—γ—裂解酶(cystuthionine—γ—lyase，CSE)mRNA表达。结果：分流组大鼠mPAP、RV／BW及RV／(LV S)比值明显高于对照组，光镜下肺小血管肌化程度明显增强，肺中、小肌型动脉相对中膜厚度明显增加。电镜下，肺中、小肌型动脉内皮细胞增生、肥厚、肿胀，平滑肌细胞增生、肥厚，并由收缩表型向合成表型转化。分流组大鼠的血浆H2S含量及肺组织CSE活性(肺组织H2S产出率)明显低于对照组，肺动脉mRNA表达明显降低。结论：肺血管结构重建是高肺血流量所致肺动脉高压的重要病理基础，内源性H2S体系——mRNA表达、CSE活性及血浆H2S含量下降可能在其形成中起重要的作用。     

Electrophysiological effects of hydrogen sulfide on human atrial fibers

Background  It has been reported that endogenous or exogenous hydrogen sulfide (H₂S) exerts physiological effects in the vertebrate cardiovascular system. We have also demonstrated that H₂S acts as an important regulator of electrophysiological properties in guinea pig papillary muscles and on pacemaker cells in sinoatrial nodes of rabbits. This study was to observe the electrophysiological effects of H₂S on human atrial fibers.

Methods  Human atrial samples were collected during cardiac surgery. Parameters of action potential in human atrial specialized fibers were recorded using a standard intracellular microelectrode technique.

Results  NaHS (H₂S donor) (50, 100 and 200 μmol/L) decreased the amplitude of action potential (APA), maximal rate of depolarization (V_max), velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF), and shortened the duration of 90% repolarization (APD₉₀) in a concentration-dependent manner. ATP-sensitive K⁺ (K_ATP) channel blocker glibenclamide (Gli, 20 μmol/L) partially blocked the effects of NaHS (100 μmol/L) on human atrial fiber cells. The L-type Ca²⁺ channel agonist Bay K8644 (0.5 μmol/L) also partially blocked the effects of NaHS (100 μmol/L). An inhibitor of cystathionine γ-lyase (CSE), DL-propargylglycine (PPG, 200 μmol/L), increased APA, V_max, VDD and RPF, and prolonged APD₉₀.

Conclusions  H₂S exerts a negative chronotropic action and accelerates the repolarization of human atrial specialized fibers, possibly as a result of increases in potassium efflux through the opening of K_ATP channels and a concomitant decrease in calcium influx. Endogenous H₂S may be generated by CSE and act as an important regulator of electrophysiological properties in human atrial fibers.

     

Hydrogen sulfide and nervous system regulation

Objective  This review discusses the current status and progress in studies on the roles of hydrogen sulfide (H₂S) in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders.

Data sources  The data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011. The search terms were “hydrogen sulfide”, “neuron”, and “neurodegenerative disorders”.

Study selection  Articles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H₂S were selected.

Results  The inhibited generation of endogenous H₂S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H₂S elicits neuroprotection in Alzheimer’s disease and Parkinson’s disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H₂S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator Cl^- channels. H₂S regulates the long-term potentiation (LTP) and GABA_B receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and glia cells.

Conclusions  These articles suggest that endogenous H₂S may regulate the toxicity of neurotoxin. H₂S not only acts as a neuroprotectant but also serves as a novel neuromodulator.

     

二氧化硫衍生物舒张大鼠离体主动脉血管环的效应及其机制研究

目的:探讨二氧化硫(sulfur dioxide, SO2)及其衍生物的舒张血管作用及其机制.方法:离体大鼠主动脉环灌流,应用去甲肾上腺素(noradrenaline, NE)预收缩主动脉环后,观察其对SO2供体--亚硫酸钠/亚硫酸氢钠混合液(Na2SO3/NaHSO3, 3:1物质的量比)的舒张反应;观察应用KATP通道阻断剂格列本脲和钙通道阻断剂尼卡地平对Na2SO3/NaHSO3血管效应的影响;观察应用内源性SO2生成酶抑制剂天冬氨酸异羟肟酸(hydroxamate,HDX)和Na2SO3/NaHSO3预孵育血管组织后NE缩血管效应的变化.结果:大鼠离体主动脉环对Na2SO3/NaHSO3呈浓度(0～12 mmol/L)依赖性的舒张反应,IC50值为(7.28±0.12) mmol/L,最大舒张率(Emax)为78.79%±3.24%.格列本脲(1×10^-6 mol/L)抑制低浓度Na2SO3/NaHSO3(≤4 mmol/L)的舒血管效应,而对高浓度(＞6 mmol/L)的舒血管效应无明显影响.经尼卡地平(1×10^-9 mol/L)预孵育的血管环对NE的收缩反应明显减弱,Na2SO3/NaHSO3则不能舒张该血管.反之,预先用HDX(1×10^-4 mol/L)孵育阻断内源性SO2生成后,血管环对NE的收缩反应增强[EC50从(6.48±0.84)×10^-7 mol/L降至(3.97±1.63)×10^-7 mol/L,P＜0.01];而用Na2SO3/NaHSO3预先孵育的血管对NE的收缩反应曲线右移[EC50从(6.48±0.84)×10^-7 mol/L升至(4.93±0.81)×10^-5 mol/L,P＜0.01].结论:SO2具有明显的舒张血管平滑肌作用,其作用机制与钙离子通道及KATP通道有关,推测机体内源性SO2具有血管功能调节意义.     

Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the cardiovascular system

Objective  Sulfur dioxide was considered to be toxic and detrimental to human health. However, this review highlights recent advances that suggest sulfur dioxide might be a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.

Data sources  The data used in this review were mainly from the studies reported in Medline and PubMed published from 1986 to 2010.

Study selection  Original articles and critical reviews selected were relevant to exogenous and endogenous sulfur dioxide.

Results  The sulfur dioxide/aspartate amino transferase pathway is endogenously generated in the cardiovascular system, and sulfur dioxide shows broad bioactive effects, such as antihypertension, vasodilation, and amelioration of vascular remodeling. A disturbed sulfur dioxide/aspartate amino transferase pathway is known to be involved in the pathogenesis of many cardiovascular diseases, such as ischemia-reperfusion injury, monocrotaline-induced pulmonary hypertension, athrosclerosis, spontaneous hypertension and hypoxic pulmonary hypertension. Furthermore, in experimental studies the prognosis of these cardiovascular diseases can be improved by targeting endogenous sulfur dioxide.

Conclusion  The findings suggest that sulfur dioxide is a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.

     

高血流肺动脉高压大鼠钙敏感受体、硫化氢及活性氧的研究

目的：探讨肺动脉钙敏感受体（CaSR）、血浆硫化氢（H2S）、肺动脉内皮细胞中活性氧（ROS）水平在肺动脉高压发生发展中的作用。方法18只SD雄性大鼠按随机数字表法分为对照组和实验组,每组9只。实验组行左肺叶切除术,对照组行假手术,术后均喂养35 d。比较两组大鼠肺动脉压力（ mPAP ）、右心室肥厚指数、血浆H2 S、肺动脉内皮细胞ROS水平和肺动脉CaSR mRNA的表达水平。结果实验组大鼠mPAP、肺动脉内皮细胞ROS水平及右心室肥厚指数、肺动脉CaSR mRNA表达均明显高于对照组（ P＜0．05）,血浆H2 S含量明显低于对照组（ P＜0．05）。结论肺高血流肺动脉高压大鼠肺动脉CaSR mRNA表达的改变和内皮细胞ROS对细胞的损伤可能通过改变内源性H2 S的产生而共同参与肺动脉高压的形成。     

高肺血流性肺动脉高压大鼠肺动脉平滑肌中钙敏感受体表达和血浆中H2S含量的检测及其意义

目的：检测钙敏感受体（CaSR）在高肺血流性肺动脉高压（PH）大鼠肺动脉平滑肌中的表达水平及血浆中H₂S含量,阐明两者在PH形成机制中的作用。方法：18只雄性SD大鼠随机分为对照组和PH组,对照组大鼠行单纯开胸,PH组大鼠行左肺切除手术。饲养35 d后,应用右心导管法分别测定各组大鼠肺动脉平均压（PAMP）,检测右心室/ 体质量(RV/ BW) 和右心室/左心室+室间隔［RV/（LV+S)］ 比值,光学显微镜观察肺血管结构的变化,分光光度法检测血浆H₂S含量,应用实时荧光定量PCR方法检测大鼠肺动脉平滑肌细胞CaSR mRNA的表达水平。结果：PH组大鼠PAMP、RV/ BW及RV/ (LV + S) 比值均明显高于对照组（P<0.05）,光镜下肺小血管肌化程度明显增强,肺中、小肌型动脉相对中膜厚度明显增加（P<0.05）。PH组大鼠肺动脉平滑肌细胞CaSR mRNA的表达水平较对照组明显增高（P<0.05）;PH组大鼠血浆中H₂S含量较对照组明显降低（P<0.05）。大鼠肺动平滑肌细胞CaSR mRNA的表达水平与血浆H2S含量呈负相关(r=－0.931,P<0.05)。结论：高肺血流时肺动脉平滑肌细胞CaSR mRNA表达的改变可能通过改变内源性H2S的产生参与PH的形成。     

敏感硫电极法在测定心血管组织细胞及血浆胱硫醚-γ-裂解酶/硫化氢的应用

目的:建立测定微量硫化氢(Hydrogen sulfide, H2S)的敏感硫电极法.方法:根据硫化氢的理化特性,应用化学反应将溶液中物理溶解和化学形式存在的硫化氢转变成硫离子(S2-),应用敏感硫电极检测微量S2-,换算出溶液中H2S,构建了敏感硫电极检测H2S的方法.并检测了大鼠及人血浆中H2S的浓度、大鼠心血管组织中内源性H2S的含量以及大鼠心血管组织和细胞胱硫醚-γ-裂解酶(cystathionine-γ-lyase, CSE)的活性.结果:敏感硫电极检测1～80 μmol/L的S2-有较好的指数相关关系,应用该方法检测到雄性和雌性大鼠血浆H2S的浓度分别为(40±4)和(41±5) μmol/L,差异无统计学意义,人类男性和女性静脉血血浆H2S浓度分别为(33±4) μmol/L 和(35±5) μmol/L,差异无统计学意义.雌、雄大鼠主动脉组织H2S的含量分别为每毫克蛋白(24±6)和(25±5) nmol,心肌组织含量分别为每毫克蛋白(19±4) 和(19±6) nmol,差异无统计学意义.采用敏感硫电极法测量主动脉组织CSE活性与传统方法测量结果差异无统计学意义,但可精确测量出血管平滑肌细胞CSE的活性.结论:敏感硫电极法可以应用于CSE/H2S信号通路的检测.     

肾上腺髓质素1-50对大鼠慢性低氧性肺动脉高压的调节作用

目的:探讨肾上腺髓质素1-50(ADM1-50)对大鼠慢性低氧性肺动脉高压和肺血管结构重建的作用及其机制.方法:20只雄性Wistar大鼠随机分为对照组(n=7)、低氧组(n=6)和低氧 ADM1-50组(n=7).对于低氧 ADMi-50组大鼠,通过皮下埋放微量渗透泵持续给予ADM1-50(300ng/h).低氧饲养2周后,以右心导管法测定肺动脉平均压(mPAP),检测右心室与左心室加室间隔的比值[RV/(LV S)],观测肺血管显微和超微结构的变化,以硝酸还原酶法测定血浆一氧化氮(NO)含量,以敏感硫电极法测量大鼠血浆中硫化氢(H2S)含量.结果:低氧2周后大鼠mPAP较对照组明显增高[(24.9±6.8)mmHg vs(14.3±2.4)mmHg,P＜0.01,1 mmHg=0.133 kPa];RV/(LV S)也较对照组明显增高[(0.318±0.054)vs(0.182±0.007],P＜0.01).肺动脉显微和超微结构发生明显改变.低氧组大鼠血浆NO和H2S含量明显低于对照组.低氧 ADM1-50组大鼠mPAP明显低于低氧组大鼠[(14.9±3.0)mmHg vs(24.9±6.8)mmHg,P＜0.01];RV/(LV S)也明显低于低氧组[(0.185±0.011)vs(0.318±0.054),P＜0.01].ADMi-50使低氧大鼠血浆NO和H2S的含量明显升高.结论:ADM1-50可能通过促进低氧大鼠体内NO和H2S的生成,对低氧性肺动脉高压和肺血管结构重建的形成发挥调节作用.     

气体信号分子在肺动脉高压发病中的作用

肺动脉高压是临床众多心肺血管疾病发生、发展中重要的病理过程,决定疾病的进展及预后.肺动脉高压又是复杂病理过程,其发病机制迄今尚未完全阐明.气体分子一氧化氮(NO)和一氧化碳(CO)以其特有的可连续产生、传播迅速、效应广泛等特点对肺循环的作用与其他器官相比更具有特殊意义,并引起科学界的广泛关注,从而开创了气体信号分子这一崭新研究领域.一直被称为有毒废气的硫化氢(H2S)可在机体内源性生成,本课题组研究了H2S在心血管系统的合成与分布、心血管生理学以及病理生理学意义,提出内源性H2S是心血管功能调节的新型气体信号分子,并揭示其对心血管疾病发病具有普遍性调节作用.通过对这3种气体信号分子在低氧性和高肺血流性肺动脉高压中的变化规律、作用环节及其分子机制的研究发现,气体信号分子体系异常是这两种肺动脉高压发病中重要发病机制之一,外源性给予气体信号分子可以缓解肺动脉高压和肺血管结构重建,其作用机制包括舒张血管、调节血管平滑肌细胞增殖/凋亡失衡、通过抑制胶原蛋白过度合成、促进胶原蛋白降解环节抑制肺动脉胶原蛋白的异常堆积,进而揭示了气体信号分子在肺动脉高压中的重要调节作用.     

硫化氢对呼吸中枢节律性的调节作用

硫化氢(H2S)已成为第三种内源性气体信号分子。H2S由胱硫醚-β-合酶、胱硫醚-γ-裂解酶和3-巯基丙酮酸转硫酶三种酶产生。呼吸节律产生于中枢神经系统脑干延髓的一个局限区域——前包钦格复合体,生理浓度的H2S对中枢性呼吸节律有"先抑制后兴奋"的双向调节作用,而高浓度H2S对呼吸节律产生抑制作用。H2S可能是通过KATP通道和环磷酸腺苷途径参与呼吸中枢节律性调控。     

Imbalance of endogenous homocysteine and hydrogen sulfide metabolic pathway in essential hypertensive children

Background  Hypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H₂S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension.
Methods  Twenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H₂S level was detected by a modified method with a sulfide electrode. Data were presented as mean±standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H₂S as well as to the systolic pressure against the plasma H₂S/Hcy ratio.
Results  Plasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H₂S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68±9.69) µmol/L vs (6.62±4.79) µmol/L (t=2.996, P<0.01); H₂S: (51.93±6.01) µmol/L vs (65.70±5.50) µmol/L) (t=-8.670, P<0.01)). The ratio of plasma H₂S/Hcy in children with hypertension was 5.83±2.91, while that of the control group was 11.60±3.30, and the difference is significant with a t=-6.610 and P<0.01. A negative correlation existed between plasma Hcy and H₂S concentrations, r=-0.379, P<0.05. And a negative correlation was found between systolic blood pressure and the plasma H₂S/Hcy ratio, r=-0.687, P<0.05.
Conclusion  There was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.

     

内源性二氧化硫在心血管系统中的生物学意义

美国科学家关于内源性气体分子一氧化氮(NO)和一氧化碳(CO)生物学效应的研究开创了生命调节的新理论。我们近年来提出在心血管功能调节中还存在第三个气体信号分子硫化氢(H2S)[1-4],这推进了生命科学领域科学研究的进步。二氧化硫(SO2)也是一种气体小分子,以往人