Regulation of angiotensinⅡon Gαq/11 protein of vascular smooth muscle cell and its underlying mechanism

To study the regulation of angiotensin Ⅱ(Ang Ⅱ) on Gαq/11 protein of vascular smooth muscle cell (VSMC) and its underlying mechanism, the protein synthesis was detected by [³H]-leucine incorporation. Gαq/11 expression was measured by Western blot in cultured VSMC of rat aorta. The results showed that the level of Gαq/11 was downregulated after stimulated by AngⅡ for 1—6 h, while it was upregulated significantly by 12—24 h stimulation (P < 0.01) in VSMC. The [³H]-leucine incorporation of VSMC was increased after 24 h Ang Ⅱ stimulation. The biphase regulation of Ang Ⅱ on Gαq/11 protein was blocked by the Ang Ⅱ type Ⅰ receptor (AT1) specific antagnist losartan or PLC inhibitor U73122, while PD98059 did not have this effect. These data indicated that Ang Ⅱ contributed to VSMC hypertrophy by regulating the level of Gαq/11, and this effect was mediated mainly through AT1 receptor-PLC signal transduction pathway.     

苦物质引起去甲肾上腺素预收缩的大鼠主动脉平滑肌舒张的作用机理研究

为研究苦物质舒张预收缩的大鼠胸主动脉平滑肌的作用机制,以测定肌张力为主要手段,结合多种细胞信号通路阻断剂研究了苦物质的作用通路.结果表明:苦物质对于去甲肾上腺素介导的大鼠胸主动脉的收缩具有高效、快速的舒张作用,此舒张作用与IP3受体和L型钙通道的阻断密切相关.故以氯喹和苦精为代表的苦物质因对血管平滑肌具有良好的舒张作用,有望成为针对高血压等血管相关疾病的新的治疗药物.     

Urotensin Ⅱ increases endothelin production by vascular smooth muscle cells in rats

The aim of this study was to observe the effects of urotensin Ⅱ (UII) on production of endothelin (ET) in rat aortic vascular smooth muscle cells (VSMC). Cultured VSMCs incubated with various concentrations of UII were used to measure the VSMC ³H-TdR incorporation, the amount of ET mRNA and ET production in VSMCs. In this work we found that UII (10^-10—10^-8 mol/L) promoted VSMC ³H-TdR incorporation (47%—83%, P < 0.01) and increased the amount of ET mRNA by 17.1% (P < 0.05) to 112.8% (P < 0.01), respectively, in a concentration dependent manner compared with control. After 4 and 8 h incubation, 10^-10—10^-8 mol/L of UII elevated the ET synthesis and release in a concentration dependent manner. After 4 h incubation, the content of ET in medium was 4.9, 5.36 and 7.12 pg/mL (P < 0.01). After 8 h incubation, the ET content released from VSMCs was 12.6, 12.07 and 17.17 pg/mL (P < 0.01). In addition, it was found that BQ₁₂₃, a specific ET_A receptor antagonist, obviously decreased the VSMC DNA synthesis induced by UII. The results of this study showed that UII could stimulate the ET mRNA expression and ET production in VSMC. The effects of UII on VSMC DNA synthesis were partly mediated by ET autocrine pathway. It suggests that the interaction between UII and ET plays an important biological regulating role as endogenous active peptides.     

Action mechanisms of a new erythrocyte-derived depressing factor

To investigate the action mechanisms of a new erythrocyte-derived depressing factor (EDDF), the focus is placed on the effect of EDDF on both cytosolic and nuclear free calcium (Ca²⁺) transportation in vascular smooth muscle cell (VSMC), as well as the apoptosis and cell cycle of VSMC of rats. EDDF has been extracted from human erythrocytes. The changes of Ca²⁺ levels in cytoplasm ([Ca²⁺]_i) and nucleus ([Ca²⁺]_n) have been observed using a laser scanning confocal microscope together with fluo-3/AM as a calcium indicator. Flow cytometric technique was used to study the effect of EDDF on cell cycle and apoptosis of VSMC. [Ca²⁺], and [Ca²⁺]_n were significantly decreased through several different pathways: ( i ) it reduced the Ca²⁺ influx by blocking L-type voltage-dependent calcium channel (L-VDC) and R-type voltage-dependent calcium channel (R-VDC); (ii) it inhibited the Ca²⁺ release from inositol 1, 4, 5-trisphosphate (IP₃) sensitive calcium store; and (iii) activated Ca²⁺-ATPase of sarcoplasmic reticulum (SR) and promoted the transportation of Ca²⁺ from cytoplasm to SR. However, EDDF seemed to have little inhibitory effect on the Ca²⁺ release from ryonodine sensitive calcium pool. It was also found that EDDF (10⁻⁴ g/mL) significantly decreased the proportion of S phase of human umbilical vein (HUV) and inhibited the proliferation of VSMC induced by angiotensin II (Angll, 10⁻⁵ mol/L). The apopotosis did not occur when VSMC was cultured under normal condition. While VSMC apoptosis was induced by Angll (10⁻⁵ mol/L) and EDDF (10⁻⁴ g/mL) seemed to have little effect on it. The inhibitory effect of EDDF on the elevation of [Ca²⁺]_i and [Ca²⁺]_n of VSMC might play an essential role in its action mechanisms and the ways it affects the Ca²⁺ handling of VSMC demonstrate that EDDF was different from other endogenous blood pressure regulators and some known antihypertensive drugs. EDDF could inhibit the proliferation of VSMC, which indicated that it might be beneficial to the prevention and treatment of hypertension and arteriosclerosis.     

Adrenomedullin inhibits the endothelin production induced by urotensin II in rat vascular smooth muscle cells

The aim of this study was to observe the effects of adrenomedullin (ADM) on endothelin (ET) production induced by urotensin Ⅱ (UⅡ) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with UⅡ (10^-8 mol/L) and with various concentrations of ADM were used to measure the VSMCs ³H-TdR incorpora- tion, the activity of extracellular signal-regulated kinase (ERK), the amount of ET mRNA and ET production in VSMCs. In this work we found that incubation with UⅡ(10^-8 mol/L) increased obviously the amount of ET mRNA in VSMCs and ET production in medium, however, coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ(10^-8 mol/L) reduced the amount of ET mRNA by 15%, 24% and 45% (P< 0.01) respectively, compared with UⅡ alone. The content of ET in medium was 14.13, 11.38 and 11.00 pg/mL. ADM alone (10^-8 mol/L) had no effect on ET production in VSMCs. UⅡ (10^-8 mol/L) promoted the 3H-TdR incorpo- ration and activity of ERK in VSMCs. ADM inhibited VSMCs 3H-TdR incorporation and activation of ERK in a concentration-dependent manner. Compared with UⅡ group, after coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ (10^-8 mol/L) the VSMCs 3H-TdR incorporation was decreased by 7% (P > 0.05), 32% (P < 0.05) and 41% (P < 0.01), respectively, and the activity of ERK was decreased by 24% (P > 0.05), 32% (P < 0.05) and 36% (P < 0.05), re- spectively, in a concentration-dependent manner. The results show that in cultured VSMCs ADM inhibits ET mRNA expression, ET production and proliferation stimulated by UⅡ, and that inhibitory effect of ADM on UⅡ bioaction could be mediated through inhibiting MAPK pathway.     

Investigation of the cross-reaction mechanism of C<Subscript>6</Subscript>H<Subscript>5</Subscript>F-HNO<Subscript>2</Subscript> aqueous solution irradiated at 355 nm by transient absorbance spectrum technique

The transient absorption spectrum technique was employed to investigate the cross-reaction mechanism of C6H5F-HNO2 aqueous solution irradiated at 355 nm. The characteristic and the kinetic parameters of transient species were also detected. Hydroxyl radical derived from the photolysis of HNO2 was added to monofluorobenzene with a second-order rate constant of （5.83±0.17）×10^9 L·mol^-1·s^-1 to form an adduct, C6H5F…OH, which was able to react with HNO2 as the main reaction pathway with a rate constant of （8.3±0.1）×10^7 L·mol^-1·s^-1. The C6F6…OH adduct can also be decayed by elimination of H2O to yield monofluorophenyl radical C6H4F-. By GC-MS technique, the final products were identified to be monofluorophenol, nitro-monofluorobenzene, nitro-monofluorophenol and para-fluorobiphenyl.     

基于TRPM8通道薄荷醇对小鼠气道平滑肌影响的实验研究

目的：基于TRPM8通道研究薄荷醇(Menthol)对小鼠气道平滑肌的影响。方法：运用平滑肌张力测定技术检测Menthol对TRPM8野生型(TRPM8+/+)和敲除型(TRPM8-/-)小鼠离体气道平滑肌的张力改变。结果：1. Menthol呈浓度依赖性地引起TRPM8+/+小鼠气道平滑肌舒张,而在TRPM8-/-小鼠此作用不明显。结论：Menthol可通过TRPM8通道改变小鼠气道平滑肌张力     

Cardiac protective role of a novel erythrocyte-derived depressing factor on rats and its Ca^2＋ mechanism

The cardiac protective role of a novel erythro-cyte-derived depressing factor (EDDF) on spontaneous hy-pertensive rats (SHR), calcium overload (CaO) rats and Wistar rats and its mechanism was evaluated. Mean artery pressure (MAP), heart rate (HR) and LVdp/dtmax were measured by physiological recorder. The effect of EDDF on the Ca2+-ATPase activity in myocardial sarcoplasmic reticu-lum (SR) of CaO rats was determined by inorganic phos-phate assay. Calcium transport in myocytes was measured by 45Ca2+ radioactive isotope measurement. The phosphoryla-tion levels of extracellular signal-regulated protein kinases (ERK1/2) in myocardial tissue of SHR and CaO rats were measured by Western blot method. And the ultrastructures of cardiac muscle cells were observed with the transmission electron microscope. The results indicated that EDDF could significantly decrease MAP, HR and LVdp/dtmax in a dose dependent manner (P < 0.05). It seems that the mechanism might relate with activating the Ca2+-APTase, enhancing the uptake and release of Ca2+ from SR (P < 0.05), decreasing the phosphorylation levels of ERK1/2 of myocytes (P < 0.01) and lightening the ultrastructural lesion of cardiac muscle cells. In CaO rats, the Ca2+-ATPase activity decreased clearly com-pared to control (64.99 7.16 vs 94.48 7.68 nmol·min-1 ·mg-1 protein, P < 0.01), while EDDF (100 mg/mL) could significantly increase the activity (87.93 ?9.54 vs 64.99 ?7.16, P < 0.05, n = 7). Both uptake and release rate of Ca2+ (祄ol 45Ca2+/g protein/min) from myocardial SR of CaO rats re-markably decreased compared to control (32.40 ?2.70 and 15.46 ?1.49 vs 61.09 ?10.89 and 25.47 ?4.29, P < 0.05); EDDF (100 mg/mL) could significantly stimulate their activi-ties (50.48 6.76 and 21.76 2.75 vs 32.40 2.70 and 15.46 1.49, P < 0.05). EDDF could evidently down-regulate the phosphorylation of ERK1/2 in myocardial tissue from SHR and CaO rats (P < 0.01), lighten the ultrastructural lesion of cardiac muscle cells of SHR as well. It is concluded that EDDF seems to play protective roles on both structure and function of heart, which closely related with amelioration of Ca2+ transport and inhibition of Ca2+-MAP kinase pathway.     

Population Characteristics and Future Population Countermeasures for the Studied Counties in Tibet, China

Focusing on the 18 counties along ““““One River and Two Tributaries““““ region, and based on the data from China 3^nd , 4th and 5^th population censuses, this article has analyzed the time and spatial changing patterns of the population in this region, The analyses show that since the 3^al population census, total population, average age and total birth rate have all changed considerably: ① Total population has grown fast, with most counties‘ annual average growth rate of more than 10. ② In terms of the region‘s average age, in 2000 the age inthe 18 counties is younger than 30 years old. ③ Compared with the 3^rd population census, labor force by the 5^th census is much younger. ④ Countermeasures are proposed to control population by controlling birth rate as the result of the local resident‘s quality improvement by education.     

铝合金PLC效应与声发射特性的实验研究

考虑退火温度和应变率对6063铝合金力学性能的影响,采用材料试验机和声发射测试系统对铝合金PLC效应和声发射特性开展实验研究,获得了不同应变率下材料的应力-应变曲线和不同退火温度下声发射参数的变化规律.结果表明,2×10-3,2×10-4,2×10-5s-1应变率加载时,6063铝合金的应力应变曲线表现出明显的PLC现象,降低加载应变率,PLC现象增强,并出现了从A型到C型的转化;加载应变率为2×10-4s-1时,PLC效应的临界应变随退火温度的升高而降低;由于细观结构上可动位错密度的增加,屈服阶段试件中产生的声发射振铃计数急剧增加,达到峰值;进入到塑性强化阶段,声发射活动减弱;弹性变形阶段和塑性强化阶段产生突发型信号,而屈服阶段为连续型信号,与试件的均匀变形以及剪切变形带的形成与传播相关.      

α-LTX and α-LTXN4C induce [Ca2+]i elevation through different mechanisms in pancreatic β cells

α-latrotoxin (α-LTX) is the only neurotoxin from black-widow spider which has secretagogue effects in the vertebrates. It causes massive neurotransmitter and hormone release via two instinct mechanisms after binding with its high-affinity membrane recep…     

Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.     

Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium

Stimulation of the endothelial lining of arteries with acetylcholine results in the release of a diffusible substance that relaxes and hyperpolarizes the underlying smooth muscle. Nitric oxide (NO) has been a candidate for this substance, termed endothelium-derived relaxing factor. But there are several observations that argue against the involvement of NO in acetylcholine-induced hyperpolarization. First, exogenous NO has no effect on the membrane potential of canine mesenteric arteries. Second, although haemoglobin (believed to bind and inactivate NO (refs 11-15)) and methylene blue (which prevents the stimulation of guanylate cyclase) inhibit relaxation, neither has an effect on hyperpolarization. Finally, nitroprusside, thought to generate NO in vascular smooth muscle, relaxes rat aorta without increasing rubidium efflux. Nevertheless, nitrovasodilators, nitroprusside and nitroglycerin cause hyperpolarization in some arteries. NO might therefore be responsible for at least part of the hyperpolarization induced by acetylcholine. We now report that hyperpolarization and relaxation evoked by acetylcholine are reduced by NG-monomethyl-L-arginine, an inhibitor of NO biosynthesis from L-arginine. Thus NO derived from the endothelium can cause hyperpolarization of vascular smooth muscle, which might also contribute to relaxation by closing voltage-dependent calcium channels. Our findings raise the possibility that hyperpolarization might be a component of NO signal transduction in neurons or inflammatory cells.     

膀胱逼尿肌的组织及生理学概述

膀胱逼尿肌在组织结构、超微结构、收缩功能、舒张功能、自律性及电生理学方面具有自身的特点.在组织结构上,通过平滑肌肌束之间的交叉聚集使膀胱逼尿肌成为一个统一的整体;在超微结构上,通过逼尿肌肌细胞之间的中间连接使平滑肌肌束成为一个有机的组合;在收缩功能上,膀胱逼尿肌的特点是自发性收缩和神经性收缩的动态平衡;在舒张功能上,膀胱逼尿肌的特点是应力性舒张和神经性舒张的协调一致;在自律性方面,膀胱逼尿肌具有产生自发性动作电位的能力以及触发自主性收缩的能力;在电生理方面,膀胱逼尿肌的肌膜去极化引起的动作电位通过作用于钙通道形成Ca2+内流,实现了兴奋与收缩之间的耦联.     

Kinetic investigation of <Emphasis Type="Italic">in situ</Emphasis> growth of CdMoO<Subscript>4</Subscript> nano-octahedra

CdMoO₄ nano-octahedra were grown in situ at room temperature by reverse-microemulsion. Energy evolution from this growth process was monitored using microcalorimetry. The microcalorimetric heat flow (MCHF) curve showed a characteristic endothermic peak for the initial reaction, and double discontinuous exothermic peaks for the subsequent crystal growth. Combined with complementary characterization techniques, the evolution of morphology and size of the CdMoO₄ nano-octahedra were correlated with the MCHF peaks. Calculations based on the microcalorimetric results at 298.15 K provided rate constants of 7.56×10⁻⁵ s⁻¹ for the reaction and nucleation process and 1.59×10⁻⁴ s⁻¹ for the crystallization process.     

Polishing technology of surface for diamond film using the method of laser ablation

Conclusion Good unity in thickness and a smooth surface of diamond film are obtained by using the methods of laser ablation and machine grind to the surface of diamond film. Compared with the machine polishing method, the polishing rate increased by over 10 times. After laser ablation and machine polishing, the thickness change and the roughness of a diamond film with 400 μm thickness and 1 cm² area are 10–15 μm and 0.05 μm, and this film is basically suitable to using in electronics.     

Indian monsoon influences altitude effect of δ~(18)O in precipitation/river water on the Tibetan Plateau

The δ^18O variation in precipitation acquired from 28 stations within the network of Tibetan Observation and Research Platform （TORP） is studied, with the focus on the altitude effect of δ^18O in river water during monsoon precipitation in an effort to understand the monsoon influence on isotopic composition in annual river water. It is found that δ^18O in precipitation on the Plateau is influenced by different moisture sources, with significant Indian monsoon influence on δ^18O composition in plateau precipitation and river water. The δ^18O of water bodies in the monsoon domain is generally more depleted than that in the westerly domain, suggesting gradual rainout of southwesterly borne marine moisture in the course of long-distance transportation and lifting over the Himalayas. The lapse rate of δ^18O in river water with altitude is the largest during monsoon precipitation, due to the increased temperature vertical gradient over the southern Plateau region controlled by monsoon circulation. The combination of δ^18O in river water in monsoon （wet） and non-monsoon （dry） seasons shows a larger lapse rate than that in non-monsoon （dry） season alone. As the altitude effect of δ^18O in precipitation and river water on the Tibetan Plateau results from the combined effect of monsoon moisture supply and westerly moisture supply, the δ^18O composition and its altitude effect on the Plateau during monsoon seasons should be considered in the reconstruction of paleoelevation of the Tibetan Plateau.     

Application of Constructed Wetlands on Wastewater Treatment for Aquaculture Ponds

A group of constructed wetlands （CWs） were applied to the recirculating aquaculture system. This study assessed the performance of CWs in treating the aquaculture wastewater, examined the water quality condition of aquaculture ponds and the growth and the survival rate of ＂target＂ species （Ictalurus punctatus and Megalobrama amblycephala）. The results showed that CWs were effective on reducing the concentrations of 5-day biochemical oxygen demand （BOD5, at 70.5%）, total suspended solids （TSS, at 81.9%）, chlorophyll a （Chl-a, at 91.9%）, ammonium （NH4^＋, at 61.5%） and nitrate nitrogen （NOa-N, at 68.0%）. Effect of CWs on phosphate （PO43 -P） removal was relatively lower （at 20.0%）. The concentrations of BODs, TSS, Chl-a, NH4^＋ and TN, TP in the recirculating culture pond were significantly lower than that in the control pond（ p〈0.05 ）. CWs could help to increase total yield, survival rate of the ＂target＂ species and significantly decrease feed conversion ratio （ p〈0.05 ）.     

Sanitary Sewage Treatment with Jet Inner-loop Bioreactor

0　IntroductionThejetloopreactorhasthecharacteristicsofbothjetandloopflow .Ononehand ,theairsuckedinisdispersedintosmallgasbubblesbecauseoftheshearingforcecausedbythehighvelocityjet,producinganincreasedinterfacialcontactbe tweengasandliquid ,thusthemasstransferefficiencyisin creased .Ontheotherhand ,aregularloopflowisformedbecauseofmutualimpetusofbothjetandair lift,thusdramaticallyim provestheperformancesofmixture ,diffusion ,masstransferandheattransferofthematerial.Withoutmechanicdriving ,the…     

Electrochemical properties of LiNi<Subscript>0.5</Subscript>Mn<Subscript>1.3</Subscript>Ti<Subscript>0.2</Subscript>O<Subscript>4</Subscript>/Li<Subscript>4</Subscript>Ti<Subscript>5</Subscript>O<Subscript>12</Subscript> cells

Spinel compounds LiNi_0.5Mn_1.3Ti_0.2O₄ (LNMTO) and Li₄Ti₅O₁₂ (LTO) were synthesized by different methods. The particle sizes of LNMTO and LTO are 0.5–2 and 0.5–0.8 μm, respectively. The LNMTO/LTO cell exhibits better electrochemical properties at both a low current rate of 0.2C and a high current rate of 1C. When the specific capacity was determined based on the mass of the LNMTO cathode, the LNMTO/LTO cell delivered 137 mA·h·g⁻¹ at 0.2C and 118.2 mA·h·g⁻¹ at 1C, and the corresponding capacity retentions after 30 cycles are 88.5% and 92.4%, respectively.