大鼠尾加压素Ⅱ收缩大鼠离体肺主动脉环与MAPK相关

目的:研究大鼠尾加压素II(U-II)对大鼠离体肺主动脉环的收缩效应及与细胞信号转导通路丝裂素活化蛋白激酶(MAPK)的关系。方法:从雄性Sprague-Dauley大鼠中分离出肺主动脉, 切成3-4 mm的血管环, 制备大鼠U-II(0.03-30 nmol/L)的浓度-效应收缩曲线, 另外, 用大鼠U-II(30 nmol/L)预收缩血管达平台期后, 加入MAPK阻断剂PD 98059, 制备PD 98059(0.1 μmol/L-10 μmol/L) 浓度-效应舒张曲线, 最后分别计算EC₅₀和E_max。结果:大鼠U-II是大鼠离体肺主动脉环的有效血管收缩剂[EC₅₀=7.95±0.40, E_max=(14.28±6.34)%, 以60 mmol KCl的收缩幅度为100%];PD 98059呈浓度依赖性舒张大鼠U-II预收缩的动脉[EC₅₀=5.91±0.45, E_max=(81.39±13.65)%]。结论：大鼠尾加压素II是大鼠肺主动脉有效的血管收缩剂, 细胞信号转导通路MAPK的激活参与其收缩效应。     

PAMP、ADM和AngⅡ在血管组织释放的相互影响

目的:探讨肾上腺髓质素前体N端20肽(PAMP)和肾上腺髓质素(ADM)与血管紧张素Ⅱ(AngⅡ)之间的相互作用关系。方法:采用离体大鼠主动脉条孵育的方法,在孵育液中分别加入不同浓度(10^-9、10^-8、10^-7 mol/L)AngⅡ,用放射免疫的方法分别测定孵育液中的PAMP、ADM浓度,以及大鼠主动脉条组织中PAMP、ADM的含量;另一组在孵育液中分别加入不同浓度( 10^-9、10^-8、10^-7mol/L)PAMP。分别测定孵育液中以及大鼠主动脉条组织中AngⅡ的含量。结果:不同浓度的AngⅡ可引起大鼠主动脉条组织中及释放于孵育液中的PAMP、ADM含量成剂量依赖性增加;不同浓度的PAMP对大鼠主动脉条组织中及释放于孵育液中的AngⅡ含量无明显影响。结论:AngⅡ可刺激主动脉组织释放和合成PAMP、ADM,此作用可能在心血管的调节中起一定作用。     

败血症休克大鼠血管L-精氨酸/一氧化氮途径的变化

目的:观察败血症休克大鼠主动脉内膜、中膜和外膜一氧化氮合成途径的改变。方法:雄性Wistar大鼠盲肠结扎并穿孔复制败血症休克模型,分别测定假手术组、早期休克组和晚期休克组大鼠主动脉内膜、中膜和外膜的亚硝酸盐(NO^-₂)含量、一氧化氮合酶(NOS)活性及L-精氨酸(L-Arg)转运;免疫组化染色检测诱导型一氧化氮合酶(iNOS)在主动脉各层的分布。结果:早期及晚期败血症休克大鼠主动脉内膜产生的NO^-₂含量、NOS活性及L-Arg转运速率均低于假手术组,而中膜和外膜的NO^-₂、NOS活性及L-Arg转运速率则显著高于假手术组,外膜增加的程度尤为显著。免疫组织化学染色显示,败血症休克时血管中膜和外膜尤其是外膜iNOS阳性染色明显较强。结论:败血症休克时血管内膜NO合成受到抑制,而中膜和外膜NO合成显著增强,这一改变与休克状态下血管中L-Arg转运、iNOS表达及其活性的变化有关。     

白杨素对大鼠主动脉舒张作用的影响

 目的: 研究白杨素(chrysin)对离体大鼠主动脉肌源性反应的影响,并探讨其作用机制。方法: 分离SD大鼠主动脉,采用离体血管环灌流装置观察chrysin对血管环的基础张力及对60 mmol/L KCl预收缩血管的舒张作用,并结合不同抑制剂处理,探讨其作用于血管环的可能机制。结果: Chrysin(10^-6 mol/L、3×10^-6 mol/L、10^-5 mol/L、3×10^-5 mol/L和10^-4 mol/L)对基础状态血管无明显影响,但对60 mmol/L KCl预收缩的血管环具有浓度依赖性舒张作用,并且去内皮组舒张作用弱于内皮完整组(P<0.05)。NOS抑制剂L-NAME(10^-4 mol/L)处理血管后,chrysin的舒张血管作用部分被抑制(P<0.05),COX抑制剂吲哚美辛(10^-5 mol/L)处理血管后无明显抑制作用。钾通道阻滞剂4-氨基吡啶(10^-3 mol/L)、氯化钡(10^-4 mol/L)、格列苯脲(10^-5 mol/L)和四乙胺(10^-3 mol/L)预孵后,chrysin舒张血管作用均被部分抑制(P<0.05)。Chrysin(10^-6 mol/L、10^-5 mol/L和10^-4 mol/L)可浓度依赖性抑制2.5 mmol/L CaCl₂引起的主动脉收缩。结论: Chrysin能够浓度依赖性舒张大鼠主动脉,其作用机制可能与促进一氧化氮释放、激活4种K⁺通道及减少细胞内钙离子浓度有关。     

HO-1参与葛根素对抗高糖诱导的大鼠血管舒张功能下降

目的： 研究葛根素对抗急性高糖刺激引起的血管舒张功能的下降,并分析血红素加氧酶（HO-1）在其中的作用。方法: 采用血管环灌流装置,观察大鼠胸主动脉环的舒张效应。结果: ①与空白对照组（含11 mmol/L葡萄糖）相比,经44 mmol/L葡萄糖（高糖）孵育血管2 h后,主动脉环对ACh引起的内皮依赖性血管舒张反应下降。②葛根素（10-10-10-8 mol/L）与高糖联合孵育,可剂量依赖性地改善高糖诱导的血管ACh舒张反应的下降。③葛根素孵育血管后可引起血管HO-1活性增高;用ZnPPIX抑制HO-1的活性后,葛根素抗高糖损伤的作用被取消。结论: 葛根素可以对抗高糖引起的血管舒张功能的下降,其机制可能是通过诱导HO-1而实现的。     

一氧化氮在休克大鼠离体淋巴管对P物质反应性中的作用

目的: 应用离体淋巴管灌流技术,观察一氧化氮(NO)在失血性休克(HS)大鼠离体淋巴管对P物质(SP)反应性双相变化中的作用。方法: Wistar雄性大鼠随机分为对照组(仅手术)和休克组(复制HS模型后分为shock 0.5 h、shock 2 h组)。在相应时点分离胸导管,制备淋巴管条,3 cmH₂O跨壁压下行离体灌流,应用一氧化氮合酶(NOS)工具药分别孵育shock 0.5 h和shock 2 h的淋巴管。分别给予从低到高浓度的SP,测量淋巴管收缩末期口径、舒张末期口径、收缩频率(CF)和被动管径,计算收缩幅度(CA)、泵流分数(FPF)和紧张指数(TI),以给予SP前后淋巴管的CF、TI、CA和FPF的差值ΔCF、ΔTI、ΔCA和ΔFPF评价淋巴管对SP的反应性。结果: NO供体L-Arg可显著降低shock 0.5 h淋巴管对多个SP浓度点的ΔCF、ΔTI与ΔFPF;可溶性鸟苷酸环化酶抑制剂ODQ可显著抑制L-Arg的作用,在某些SP浓度点上,使ΔCF、ΔTI和ΔFPF显著高于shock 0.5 h+L-Arg组,ΔCF和ΔFPF高于对照组水平。NOS抑制剂L-NAME可提高shock 2 h淋巴管对多个SP浓度点的ΔCF、ΔTI与ΔFPF,且高于对照组水平;shock 2 h淋巴管与L-NAME和磷酸二酯酶抑制剂氨茶碱(AP)同时孵育后,在SP为1×10^-8 mol/L和3×10^-8 mol/L时,AP显著抑制了L-NAME的作用,使ΔCF、ΔTI与ΔFPF明显降低。结论: NO参与了休克淋巴管反应性的双相调节,其机制可能是通过环鸟苷酸实现的。     

内源性CO/NO在CCK-8逆转内毒素血症大鼠低血管反应性中的作用

目的:探讨HO-1-CO-cGMP和NOS-NO-cGMP细胞信号转导通路在八肽胆囊收缩素(CCK-8)逆转内毒素血症大鼠低血管反应性中的作用。方法:按照整体用药将大鼠分为4组:对照组、LPS组、CCK组及CCK+LPS组;用离体血管环张力测定技术,观察胸主动脉环(TARs)对苯肾上腺素(PE)累积收缩反应;分别用一氧化碳(CO)供体正铁血红素(He)、血红素氧合酶1(HO-1)抑制剂锌原卟啉(ZnPP-IX)、一氧化氮合酶(NOS)底物L-精氨酸(L-Arg)、诱生型一氧化氮合酶(iNOS)选择性抑制剂氨基胍(AG)、NOS抑制剂N^ω-硝基-L-精氨酸(L-NNA)、鸟苷酸环化酶(sGC)抑制剂亚甲兰(MB)预孵育后,测定TARs对PE的收缩反应。结果:单独应用CCK-8对血管张力无明显影响;预先注射CCK-8可明显逆转LPS所致的低血管反应性;LPS及CCK+LPS组TARs用ZnPP-IX或AG孵育,可部分逆转这种低血管反应性;经L-NNA或MB孵育,可使低血管反应恢复正常;用He或L-Arg孵育可不同程度加重低血管反应状态。结论:CCK-8本身不激活HO-1和iNOS,但可影响LPS诱导的HO-1和iNOS活性上升,减少CO/NO合成,从而使cGMP含量下降,对逆转内毒素血症大鼠低血管反应性有重要作用。     

感染性休克下调大鼠血管内皮和血小板L-精氨酸/一氧化氮通路

目的：观察感染性休克对大鼠血小板及血管L-精氨酸(L-Arg)/一氧化氮合酶(NOS) /一氧化氮(NO)通路的影响及其相互联系,探讨感染性休克损伤的机制。方法:利用盲肠结扎并穿孔复制早期和晚期感染性休克大鼠模型,采用Greiss法测定血管各层及血小板孵育液亚硝酸盐(NO^-₂/NO^-₃)含量;以同位素示踪法检测其NOS活性及L -Arg转运。结果:早、晚期感染性休克大鼠血小板和主动脉内膜NO-2/NO-3水平、NOS 活性及低亲合L-Arg 转运量均显著低于假手术组(高亲合L- Arg 转运量在早期休克增加、晚期休克降低);而中膜和外膜的NO^-₂/NO^-₃水平、NOS 活性及L-Arg 转运量则显著高于假手术组,均以休克晚期改变为显著。血小板和主动脉内膜NO^-₂/NO^-₃生成、NOS 活性及高、低亲合L-Arg 转运的改变均呈正相关(均P< 0. 01)。结论:感染性休克下调血管内膜和血小板的L-Arg/NO通路,上调血管中膜和外膜L-Arg/ NO通路。提示检测血小板L-Arg/NO通路的变化可能反映休克时血管内皮功能的损伤。     

一氧化氮对成纤维细胞内游离Ca2+浓度的影响

目的: 研究一氧化氮(NO)对成纤维细胞内游离Ca²⁺浓度的影响。方法: 体外培养人胚肺成纤维细胞(HLF), 给予NO前体-L-精氨酸(L-Arg)及一氧化氮合酶(NOS)抑制剂-硝基-L-精氨酸(L-NNA), 采用比色法测定细胞培养液NO水平, 采用Fura-2/AM荧光法测定细胞内游离Ca²⁺浓度, 观察NO对成纤维细胞内游离Ca²⁺浓度的影响。结果: 随着细胞培养液NO水平逐渐升高, 成纤维细胞内游离Ca²⁺浓度逐渐升高[实验组NO水平、Ca²⁺ 浓度比正常对照组NO水平、Ca²⁺浓度分别为(3.82±0.53) mol/L比(2.62±0.55) mol/L和(894.48±93.01) nmol/L比(824.56±33.22) nmol/L, P<0.05]; 但进一步升高NO水平, Ca²⁺浓度却逐渐降低[实验组NO水平、Ca²⁺浓度比正常对照组NO水平、Ca²⁺浓度分别为(5.82±0.45) mol/L比(2.62±0.55) mol/L和(162.11±68.50) nmol/L比(824.56±33.22) nmol/L, P<0.01]。结论: NO对成纤维细胞内游离Ca²⁺浓度具有双向调节作用。即低水平NO升高细胞内游离Ca²⁺浓度, 高水平NO降低细胞内游离Ca²⁺浓度。     

NO、CO在LPS诱导的离体兔肺动脉舒张反应下降中的作用

目的:探讨脂多糖(LPS)所致离体肺动脉反应性张力变化与肺动脉内源性一氧化氮( NO)、一氧化碳(CO)的关系.方法:制备离体兔肺动脉环.①对照组,培养基中加入生理盐水溶剂;②LPS组,培养基中加入LPS 4 μg/mL.两组孵育7 h,检测肺动脉环对10-6 mol/L新福林(PE)的收缩反应及对l0-6 mol/L乙酰胆碱(ACh)的内皮依赖性舒张反应,以及一氧化氮合酶(NOS) 抑制剂氨基胍(AG)和N+-硝基-L-精氨酸(L-NNA),血红素氧合酶-l(HO-1)抑制剂锌卟啉原(ZnPP)预孵育20 min后,肺动脉环对PE及ACh反应性的改变.结果:①LP S孵育7 h时肺动脉环对ACh的内皮依赖性舒张百分比显著低于对照组(P＜0.05),而不影响肺动脉环对PE的收缩反应;②两组用10-4 mol/L AG、10-5 mol/L ZnPP预孵育20 min后,LPS组对 ACh的舒张百分比显著降低,对PE的收缩值显著增加(均P值＜0.01),对照组对ACh的舒张百分比均无显著改变. 10-4 mol/L-NNA预孵育20 min后,两组对ACh反应均表现收缩,对PE的收缩反应较孵育前(对照)均显著增加(P＜0.01),而与AG孵育后的PE收缩值比较,LPS组无显著差异,对照组显著增加.讨论:内皮源性NO在血管张力的调控上起重要作用,ACh为内皮依赖及受体依赖性舒血管物质,内皮源性NO介导其舒张反应.实验结果表明,LPS孵育后,肺动脉内皮依赖性舒张反应显著降低,对PE收缩反应无明显变化,提示LPS可能直接损伤了肺动脉内皮细胞功能, 如抑制cNOS活性,妨碍NO生成与释放;AG预孵育后LPS组对PE收缩显著增强,提示,LPS可引起iNOS诱生;ZnPP预孵育后LPS组收缩反应显著增强,ACh舒张百分比下降,溶剂对照组收缩反应也增强,但ACh舒张百分比与孵育前比较无显著差异.提示:CO参与生理和病理情况下的血管张力的调控.结论:①LPS可导致离体兔肺动脉内皮依赖性舒张反应减弱;②LPS对肺血管的损伤作用与NO有关,提示LPS可使内皮cNOS活性下降,CO在LPS损伤中起一定的作用,但其与NO的关系有待于进一步探讨.     

菊米提取液舒张血管作用及其机制研究

目的： 研究菊米的舒张血管作用以及其作用机制。 方法： 采用血管环灌流装置测定离体大鼠胸主动脉环的血管舒张效应。 结果： 菊米提取液（0.5-8 g/L）可引起主动脉环发生浓度依赖性舒张。且内皮完整组的舒张程度明显大于去内皮组。用L-NAME或KCl（20 mmol/L）孵育内皮完整的血管环后，可明显抑制菊米提取液引发的血管舒张。去内皮的血管环用L-NAME孵育后，菊米提取液引发的血管舒张作用明显减弱。含有完整内皮或去内皮的胸主动脉用菊米提取液（8 g/L）孵育30 min后，组织中NOS的活性均大于未用菊米提取液孵育的对照组。结论： 菊米提取液可引起血管发生内皮依赖性和非内皮依赖性的舒张作用。其作用机制可能与增加NOS活性和内皮细胞超极化因子（EDHF）释放增加有关。     

Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta

The goal of this in vitro study was to examine the effects of pre-acidification and pre-akalinization on the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in isolated rat aorta. Isolated aortic rings with and without the nitric oxide synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME) were exposed to four types of Krebs solution (pH 7.0, 7.2, 7.4, and 7.6), followed by the addition of 60 mM potassium chloride. When the toxic dose of levobupivacaine (3 × 10^-4 M) produced a stable and sustained vasodilation in the isolated aortic rings that were precontracted with 60 mM potassium chloride, increasing lipid emulsion concentrations (SMOFlipid^®: 0.24, 0.48, 0.95 and 1.39%) were added to generate concentration-response curves. The effects of mild pre-acidification alone and mild pre-acidification in combination with a lipid emulsion on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells were investigated by Western blotting. Mild pre-acidification caused by the pH 7.2 Krebs solution enhanced the lipid emulsion-mediated reversal of levobupivacaine-induced vasodilation in isolated endothelium-intact aortic rings, whereas mild pre-acidification caused by the pH 7.2 Krebs solution did not significantly alter the lipid emulsion-mediated reversal of the levobupivacaine-induced vasodilation in isolated endothelium-denuded aortic rings or endothelium-intact aortic rings with L-NAME. A lipid emulsion attenuated the increased eNOS phosphorylation induced by the pH 7.2 Krebs solution. Taken together, these results suggest that mild pre-acidification enhances the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in the endothelium-intact aorta via the inhibition of nitric oxide.     

Effect of phenylephrine and endothelium on vasomotion in rat aorta involves potassium uptake

Vasomotion is defined as the rhythmic contractions in blood vessels, consisting of two components: vasoconstriction and oscillations of the plasma membrane potential. To determine whether vasomotion is associated with changes in K⁺ uptake, we measured the effect of phenylephrine (PE) and acetylcholine (ACh) on the K⁺ uptake and vascular reactivity in rat aortic rings. We found that the incubation of aortic rings with 10^?7 M PE (210 ± 28 mg maximum amplitude), and 10^?6 M ACh (177 ± 6 mg maximum amplitude) produced the highest rhythmic contractions. Both 10^?7 M PE and 10^?6 M ACh significantly increased K⁺ uptake in endothelium-intact aorta versus control (121 % PE, 117 % ACh). Removal of the endothelium blunted rhythmic contractions and decreased K⁺ uptake in presence of vasoactive substances (88 % PE, 81 % ACh). The inhibition of nitric oxide synthase with 10^?4 M l-NNA significantly reduced the rhythmic contractions, and it was reversed in the presence of 10^?8 M sodium nitroprusside (SNP; a nitric oxide donor). Also, we found that 10^?4 M l-NNA significantly decreased the effect of 10^?7 M PE on K⁺ uptake in aortic rings (104 % PE + l-NNA vs. control). The incubation of endothelium-denuded rings with 10^?8 M SNP significantly increased the K⁺ uptake (116 % SNP vs. control), similar to those observed in the presence of 10^?6 M ACh. The inhibition of protein kinase G with KT-5823 blocked SNP-mediated increase in K⁺ uptake. In conclusion, these data suggest that a certain range of K⁺ uptake is necessary to induce the rhythmic contractions in response to vasoactive substances.     

Replacement of connexin 43 by connexin 32 in a knock-in mice model attenuates aortic endothelium-derived hyperpolarizing factor-mediated relaxation

Previous studies demonstrated that intercellular communication through endothelial, smooth muscle or myoendothelial connexin channels contributes to the control of vascular tone. At least four connexin types are present in the arterial wall. The aim of the present work was to assess the role played by connexin 43 (Cx43)-formed gap junctions on vessel function. Aortic reactivity to noradrenaline, acetylcholine and sodium nitroprusside, and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations, were analysed in a Cx43KI32 mouse model in which the coding region of Cx43 was replaced by that of connexin 32 (Cx32). Aortic rings were placed in organ baths containing a Krebs solution oxygenated at 37°C (pH 7.4). Confocal images of aortic rings confirmed connexin substitution in mutant mice. In control conditions, replacement of Cx43 by Cx32 in homozygous mutant mice did not modify endothelium-independent contractile responses to noradrenaline, or relaxations in response to sodium nitroprusside (endothelium independent) or acetylcholine (endothelium dependent). However, residual endothelium-dependent relaxations in response to acetylcholine after nitric oxide synthase and cyclooxygenase inhibition (EDHF type) were significantly reduced in homozygous Cx43KI32 mice (maximal effect values: 4.86 ± 0.37% of noradrenaline precontraction versus 7.06 ± 0.31% in wild-type, n = 8, P < 0.05). This attenuation was mimicked by treatment of rings from wild-type animals with the connexin-mimetic peptide ^37,43Gap27 (5 × 10⁻⁶ m ). In conclusion, replacement of Cx43 by Cx32 attenuates EDHF-mediated relaxations in mice aortic rings, suggesting that they are, at least in part, dependent on Cx43-formed gap junctions. In contrast, aortic responses to tested endothelium-independent agonists were not modified in knock-in animals.     

Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium‐dependent vasodilation in the femoral artery of developing piglets

Mechanisms mediating endothelium‐dependent vasodilation were investigated in femoral artery rings from <2‐day‐old (newborn) and 2‐week‐old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)‐cyclic 3′,5′‐guanosine monophosphate (cGMP) and K⁺ channel‐activation to acetylcholine (ACh)‐induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K⁺ channel blockade and the intra‐arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS‐inhibitors N ^G‐monomethyl‐L ‐arginine acetate (L ‐NMMA; 100 μM ) or N^G‐nitro‐L ‐arginine (L ‐NOARG; 1–100 μM ), however, relaxation was significantly more reduced in femoral artery rings from 2‐week‐old than from newborn, with lower pD₂ values in the older age group. Inhibition of large (BK_Ca) conductance calcium‐sensitive K⁺ channels with tetraethylammonium chloride (TEA; 1 mM ), gave a significant rightward shift in the concentration‐response curves to ACh which was of the same magnitude in both age groups. The ACh‐induced vasodilation was abolished in both age groups by high K⁺ (20 mM ) in combination with L ‐NOARG (100 μM ). The relative increase in cGMP levels after addition of ACh (10 nM ) was significantly larger in rings from newborn compared with 2‐week‐old piglets (12‐ vs. four‐fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K⁺ channel blockade with TEA was the same in femoral artery rings from newborn to 2‐week‐old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.     

Impaired EDHF-mediated vasodilatation in adult offspring of rats exposed to a fat-rich diet in pregnancy

We recently reported vascular dysfunction in adult offspring of rats fed a fat-rich (animal lard) diet in pregnancy. This study reports further characterization of constrictor and dilator function in mesenteric and caudal femoral arteries from 180-day-old offspring of dams fed the high fat diet (OHF). Endothelium-dependent relaxation in response to acetylcholine (10⁻⁹–10⁻⁵ m ) was impaired in mesenteric small arteries from male and female OHF compared with offspring of dams fed normal chow (males (maximum percentage relaxation): OHF 67.92 ± 2.89, n = 8 versus control 92.08 ± 2.19, n = 8, P < 0.01). Substantial relaxation in response to acetycholine in control mesenteric arteries remained after inhibition of nitric oxide synthase, soluble guanylate cyclase and cyclo-oxygenase but was blocked by 25 m m potassium. This component of relaxation, attributed to EDHF, was significantly reduced in OHF mesenteric arteries compared with controls. However, EDHF played a minor role in acetylcholine-induced relaxation in both control and OHF femoral caudal arteries (male and female). In these arteries, in contrast to mesenteric vessels, acetylcholine-induced relaxation was significantly enhanced in OHF but only in males (ACh (maximum percentage relaxation): OHF 58.40 ± 4.39, n = 8 versus male controls 32.18 ± 6.36, P < 0.05). This was attributable to enhanced nitric oxide-mediated relaxation. In conclusion, reduced endothelium-dependent relaxation in OHF mesenteric arteries is due to impaired EDHF-mediated relaxation. This defect was not apparent in femoral arteries in which EDHF has a less prominent role.     

碱性成纤维细胞生长因子对兔血管舒张功能及左旋精氨酸/一氧化氮途径的影响

目的：本文观察了碱性成纤维细胞生长因子（ｂＦＧＦ）对离体主动脉舒张反应,一氧化氮（ＮＯ）生成及左旋精氨酸（Ｌ－Ａｒｇ）转运的影响。方法：离体大鼠主动脉环测定张力,主动脉薄片孵育测定ＮＯ生成和Ｌ－精氨酸（Ｌ－Ａｒｇ）转运。结果：ｂＦＧＦ呈剂量依赖性地诱导血管内皮依赖性舒张,增加血管低亲和Ｌ－Ａｒｇ的最大转运速度（与对照组比较增加４５％,Ｐ＜０．０１）,显著增加ＮＯ的产生（比对照组增加４３％）。结论：ｂＦＧＦ可增加Ｌ－Ａｒｇ转运,对内皮衍生舒张因子／一氧化氮（ＥＤＲＦ／ＮＯ）系统具有重要的调节作用     

The endothelium mediates a nitric oxide-independent hyperpolarization and relaxation in the rat hepatic artery

The rat hepatic artery responds to acetylcholine (ACh) with an endothelium-dependent relaxation, which is unaffected by nitric oxide (NO) synthase and cyclooxygenase inhibition. The purpose of this study was to investigate whether the NO-independent relaxation is caused by hyperpolarization of the smooth muscle cells. In vessels with endothelium ACh induced a hyperpolarization in the presence of 0.3 mM Nw-nitro-l -arginine (l -NOARG) and 10μm indomethacin. The hyperpolarization, which slowly decayed after an initial maximum, generally lasted for at least 20 min. ACh in contrast to levcromakalim failed to hyperpolarize the smooth muscle cells in endothelium-denuded vessels. In vessels contracted by phenylephrine (PhE) ACh caused a concentration-dependent hyperpolarization and relaxation, and both events occurred over the same concentration interval. Curve fitting using the Hill equation showed a close correlation between the hyperpolarization and the relaxation. Exposure to a 30 mM K⁺ solution abolished the hyperpolarization and suppressed the relaxation induced by ACh. Nimodipine did not affect the ACh-induced hyperpolarization, whereas the relaxation induced by ACh and levcromakalim, but not that evoked by the NO donor 3-morpholino-sydnonimin, were attenuated. Glibenclamide had no effect on the ACh-induced hyperpolarization and relaxation, but abolished the corresponding responses to levcromakalim. The results demonstrate a NO-independent hyperpolarization and relaxation in the rat hepatic artery. The hyperpolarization and relaxation were endothelium-dependent, and apparently causally related to each other, since interference with the hyperpolarization or the subsequent effector pathway inhibited the relaxation.     

Endothelial factors involved in the bradykinin-induced relaxation of the guinea-pig aorta.

Endothelial factors involved in the bradykinin (BK)-induced relaxation of the guinea-pig aorta were investigated using isolated aortic rings. In intact aortic rings, higher concentrations of BK (> or = 10(-7) M) produced contraction, possibly as a direct action on smooth muscle. This BK-induced contraction was enhanced either by Nw-nitro-L-arginine (NOLA), an inhibitor of the production of nitric oxide or by indomethacin (IND), an inhibitor of cyclooxygenase, but not by carbenoxolone (CX), a known inhibitor of gap junctions. In aortic rings contracted with noradrenaline, BK elicited a relaxation with two components; an initial fast relaxation followed by a gradually diminishing slow relaxation, both in an endothelium-dependent manner. The BK-induced relaxation was inhibited in a drug specific manner by either NOLA, IND or CX. NOLA either abolished the fast relaxation, or sometimes converted it into a contractile response. IND reduced the amplitude and duration of the relaxation, by inhibiting the fast relaxation and abolishing the following slow relaxation. CX reduced both components of the relaxation. In the presence of both NOLA and CX, the BK-induced relaxation was converted to a contractile response followed by an IND-sensitive slow relaxation. In the presence of NOLA and IND together, BK stimulation caused a contraction with no following relaxation. These results indicate that in aortic rings of the guinea-pig, BK stimulates endothelial cells to release nitric oxide and prostanoids that produce the fast and slow components of the relaxation respectively. The effects of CX suggest that the contribution of EDHF to the BK-induced relaxation is weak.     

ERK1/2及JNK参与DL0805抑制血管紧张素Ⅱ引起的大鼠离体胸主动脉环收缩

目的研究Rho激酶抑制剂DL0805对血管紧张素Ⅱ(AngⅡ)引起的大鼠离体胸主动脉环收缩反应的影响及其可能的机制。方法测定离体血管张力观察大鼠胸主动脉环收缩反应,Western blot检测大鼠离体胸主动脉环ERK1/2和JNK蛋白磷酸化,和AngⅡ1型受体(AT1R)蛋白表达水平。结果 DL0805(10、25和50μmol/L)浓度依赖性地抑制AngⅡ(100 nmol/L)引起的内皮完整或去内皮的大鼠离体胸主动脉环收缩(P<0.01,P<0.001),DL0805(25和50μmol/L)抑制AngⅡ(100 nmol/L)诱导的ERK1/2和JNK的活化(P<0.05,P<0.01和P<0.001),但DL0805(5、25和50μmol/L)对AngⅡ刺激的血管环AT1R蛋白表达水平无显著影响。结论 DL0805抑制AngⅡ引起的大鼠离体胸主动脉环收缩,其机制可能与其抑制AngⅡ诱导的ERK1/2和JNK活化有关。