MCI-154对失血性休克大鼠血管平滑肌钙敏感性的影响及其机制

【目的 探讨新型钙增敏剂MCI-154对失血性休克大鼠血管平滑肌钙敏感性的影响及其可能 的机制。方法取失血性休克大鼠肠系膜上动脉(SMA),利用离体血管环张力测定技术,用去极化状态下 (120 mmol／L K+)血管环对梯度浓度Ca2+的反应来反映钙敏感性。实验分两部分:第一部分观察MCI-154 对失血性休克大鼠血管平滑肌钙敏感性的影响,第二部分观察MCI-154影响失血性休克血管平滑肌钙敏感 性与Rho-激酶、蛋白激酶C(PKC)、蛋白激酶G(PKG)的关系。结果 失血性休克后SMA血管环对Ca2+的 量-效曲线明显右移,最大收缩力(Emax)较正常组显著降低(P<0.01),MCI-154可使休克SMA血管环对 Caz+的量-效曲线进一步右移,且呈一定的剂量依赖关系,提示休克后SMA存在钙失敏,MCI-154进一步降 低休克后SMA血管环的钙敏感性。MCI-154可使具有Rho-激酶激动作用的血管紧张紊Ⅱ(Ang Ⅱ)和 PKC激动剂佛波醇-12-豆蔻酸-13-乙酸酯(PMA)作用下Ca2+的量-效曲线明显右移,Emax显著降低 (P<0.01);PKG的拮抗剂KT-5823可使MCI-154对Ca2+的量-效曲线明显左移,Emax显著升高 (P<0.01),提示MCI-154降低休克后血管平滑肌钙敏感性可能与Rho-激酶、PKC、PKG有关。结论 失血 性休克可使血管平滑肌钙敏感性降低,MCI-154可进一步降低这种钙敏感性。其机制可能通     

失血性休克大鼠血管平滑肌钙敏感性变化及其在休克双相血管反应性变化中的作用

目的观察失血性休克后血管平滑肌钙敏感性是否存在双相变化,以及钙敏感性的双相变化与血管反应性双相变化的关系。方法取失血性休克大鼠肠系膜上动脉(SMA),采用离体血管环张力测定技术,观察在失血性休克后不同时间点(休克即刻、休克30min、休克1h、休克2h)大鼠SMA血管环对梯度浓度去甲肾上腺素(NE)的收缩反应性,以及在去极化状态下(120mmol/LK+)血管环对梯度浓度钙的收缩反应性变化(钙敏感性),分析血管反应性变化与钙敏感性变化的关系;同时观察钙敏感性增强剂血管紧张素(Ang)和钙敏感性抑制剂胰岛素对血管反应性的影响。结果休克早期(即休克即刻和休克30min时)SMA对NE和钙的反应性明显升高,量效曲线明显左移,最大收缩力(Emax)明显升高(P均<0.05);随着休克时间的延长,血管环对NE和钙的反应性均逐渐下降,到休克2h均已明显降低,其量效曲线明显右移,E-max明显降低(P<0.05或P<0.01);休克后不同时间点血管反应性变化与钙敏感性变化呈显著正相关(r=0.9624,P<0.05)。具有钙敏感性增强作用的Ang(1×10-9mol/L)可明显升高休克2h血管环对NE和钙的反应性(P<0.05或P<0.01),而有钙敏感性抑制作用的胰岛素则可降低休克早期(休克即刻)血管环对NE和钙的反应性(P<0.05或P<0.01)。结论失血性休克血管平滑肌细胞存在钙敏感性的双相变化,血管平滑肌细胞钙敏感性双相变化在失血性休克血管反应性的双相变化中起重要作用。     

精氨酸血管加压素恢复失血性休克大鼠血管反应性和钙敏感性与蛋白激酶C亚型的关系

目的 探讨精氨酸血管加压素(AVP)对失血性休克大鼠血管反应性和钙敏感性的恢复作用与蛋白激酶C(PKC)亚型的关系.方法 取失血性休克大鼠肠系膜上动脉(SMA)并去除内皮,利用离体血管环张力测定技术,观察了AVP(5×10-11、5×10-10和5×10-9 mol/L)调节对休克SMA对去甲肾上腺素(NE)反应性和钙敏感性的作用及其与PKCα、δ亚型的关系.结果 AVP(5×10-11、5×10-10和5×10-9 mol/L)可明显恢复休克后的血管反应性和钙敏感性,使SMA对NE和Ca2+的量一效曲线明显左移,血管环产生的最大收缩张力(Emax)升高(P均＜0.01),且呈一定的剂量依赖关系,各剂量组间比较差异均有统计学意义(P均＜0.05).而特异性的PKCα、δ亚型抑制剂G66976(5×10-6 mol/L)和Rottlerin(10-5 mol/L)均可拮抗AVP(5×10-10 mol/L)诱导的休克后血管反应性和钙敏感性升高,抵消了AVP诱导的NE和Ca2+的量一效曲线左移,使NE的Emax明显降低(P＜0.05或P＜0.01).结论 AVP能剂量依赖性地升高失血性休克大鼠的血管反应性和血管平滑肌钙敏感性,其机制可能与PKCα、δ亚型激活有关.     

钙失敏在大鼠失血性休克血管低反应性中的作用

目的观察血管平滑肌钙失敏在大鼠失血性休克(HS)血管低反应性中的作用。方法 取失血 性休克大鼠肠系膜上动脉(SMA),利用离体血管环张力测定技术,以血管环对梯度浓度去甲肾上腺素(NE) 的收缩力反映血管反应性,用去极化状态下(120 mmol／L K+)血管环对梯度浓度Ca2+的收缩力反映血管的 钙敏感性,观察失血性休克低反应血管是否存在钙敏感性降低以及钙敏感性调节剂血管紧张素Ⅱ(Ang Ⅱ)、 胰岛素以及Rho-激酶特异性抑制剂Fasudil是否可以通过调节钙敏感性来调节血管反应性。结果 失血性 休克后SMA对NE的反应性和钙敏感性均显著下降,表现为NE的量-效曲线明显右移,NE的最大收缩力 (Emax)和-lg[EC50](pD2)降低(P<0.05或P<0.01);Ca2+的量一效曲线明显右移,Ca2+的Emax和pD2降低 (P<0.05或P<0.01)。具有钙敏感性增强作用的Ang Ⅱ(10-9mol／L)可使NE和Ca2+的量-效曲线左移,使 NE和Ca2+的Emax增高(P<0.05或P<0.01)。而具有钙敏感性抑制作用的胰岛素(100 nmol／L)可使NE 和Ca2+的量-效曲线右移,NE和Ca2+的Emax降低(P<0.05或P<0.01).Fasudil预处理可消除Ang Ⅱ对 NE诱导的血管收缩反应的增强效果,降低钙敏感性。结论 失血性休克血管平滑肌细胞存在钙敏感性降低. 血管平滑肌细胞钙敏感性降低在失血性休克血管低反应性的     

蛋白激酶Cε对失血性休克大鼠血管反应性和钙敏感性的调节作用

目的 观察蛋白激酶Cε(PKCε)对失血性休克血管反应性和钙敏感性的调节作用.方法 取失血性休克大鼠肠系膜上动脉,利用逆转录一聚合酶链反应(RT-PCR)测定休克即时、0.5、1、2和4 h PKCε mRNA的表达;取大鼠肠系膜上动脉一级分支,利用离体血管张力测定技术,测定不同休克时间点的血管环反应性和钙敏感性,并观察PKCε的激动剂和抑制剂对休克2 h血管反应性和钙敏感性的影响.结果 ①大鼠血管反应性和钙敏感性在休克早期增高,晚期进行性降低;正常组织PKCε mRNA表达量低,失血性休克后表达逐渐增加,于1 h达到峰值(P＜0.01),4 h时仍维持在较高水平(P＜0.01).②PKCε的激动剂可增高休克2 h的血管反应性和钙敏感性,PKCε的抑制剂可降低休克2 h的血管反应性和钙敏感性(P均＜0.01).结论 PKCε对失血性休克血管反应性和钙敏感性有重要的调节作用,可能是一种重要的内源性保护分子.     

失血性休克大鼠PKCα mRNA表达变化规律及对血管低反应性的调节作用

目的 观察PKCot在大鼠失血性休克血管平滑肌中mRNA表达变化规律,及其对失血性休克血管反应性和钙敏感性的调控作用.方法 采用PCR技术测定大鼠肠系膜上动脉不同休克时间点(休克即时、30 min、1 h、2 h、4 h)的PKCct mRNA表达;用离体血管环张力测定技术观察不同休克时间点的肠系膜上动脉一级分支的血管环反应性和钙敏感性变化,以及PKCa激动剂和抑制剂对休克2 h血管反应性、钙敏感性的影响.结果 ①失血性休克后大鼠血管反应性和钙敏感性早期增高、晚期降低,PKCot mRNA表达逐渐增高,于1 h达到峰值(P<0.01),4 h时仍处于较高水平(P<0.01).②PKCa激动剂和抑制剂可分别增高和降低休克2 h大鼠的血管反应性和钙敏感性.结论 PKCct在失血性休克血管反应性和钙敏感性调控中起重要作用,可能是休克血管功能的重要保护性分子.     

血管生成素-1,2经p38丝裂原活化蛋白激酶调节失血性休克血管低反应性

目的 观察p38丝裂原活化蛋白激酶(p38MAPK)在血管生成素-1(Ang-1)、血管生成素-2(Ang-2)调节失血性休克大鼠血管反应性双相变化中的作用.方法 观察失血性休克后不同时间点肠系膜上动脉(SMA)中p38MAPK蛋白表达和磷酸化变化,p38MAPK抑制剂对Ang-1和Ang-2调节缺氧早期和晚期血管反应性作用的影响,以及给予Ang-1、Ang-2和Tie-1抑制剂后缺氧血管内皮细胞(VEC)和血管平滑肌细胞(VSMC)混合细胞中p38MAPK蛋白表达和磷酸化变化.结果 失血性休克后p38MAPK磷酸化水平显著增高;p38MAPK抑制剂可显著改善缺氧4 h血管低反应性并拮抗Ang-2进一步降低缺氧4 h血管低反应性的作用;Ang-1和Tie-2抑制剂可显著抑制缺氧4 h的p38MAPK磷酸化增高(P<0.01).结论 p38MAPK参与了Ang-1和Ang-2对休克晚期血管低反应性的调节,但不是休克早期血管高反应性的主要调节分子.     

失血性休克并发急性肺损伤大鼠蛋白激酶C的表达

目的 探讨蛋白激酶C（PKC）在失血性休克并发急性肺损伤动物体内的变化与意义.方法 健康成年雄性SD大鼠40只,随机分为对照组,失血性休克组和失血性休克＋内毒素组,以大鼠失血性休克时LPS所致ALI为模型,采用酶联免疫吸附（ELISA）法检测血清TNF-α、IL-1β及IL-6,Westernblot检测肺组织TLR4与PKC的蛋白表达,EMSA检测NF-κB活性变化,观察肺脏含水量、肺脏病理变化.结果 失血性休克早期即可发生肺血管通透性增高,肺脏含水量上升,组织学检查显示肺脏出现明显的病理损害,肺组织PKC与NF-κB DNA活性、TLR4同步增强,尤以内毒素作用后为著.结论 PKC的活化参与了失血性休克时ALI的发病,即TLRs/NF-κB信号通路的活化.     

血管钙化对大鼠离体胸主动脉环张力的影响

目的　在大鼠血管钙化模型上,观察血管钙化时对血管张力的直接影响,并探讨其作用机制。方法　维生素D3 (Vit D3)和尼古丁(nicotine)诱导大鼠血管钙化模型,通过BL-Newcentrary型多导生理记录仪,观察钙化大鼠离体胸主动脉环对去甲肾上腺素(norepinephine,NE,10-8～ 10-4 mol/L)和乙酰胆碱(acetylcholine,ACh, 10-8～ 10-4 mol/L)引起的收缩和舒张反应。结果　钙化血管Von Kossa 染色见钙化组血管的中膜弹性纤维间可见大量黑色颗粒, 沉积于细胞外基质和平滑肌细胞内,表明存在钙沉积。主动脉钙含量和碱性磷酸酶（alkaline phosphatase,ALP）活性分别较对照组高6.8 倍和1.9倍( P < 0.01) , 与对照组相比,钙化大鼠胸主动脉环对N E 的缩血管反应和对ACh的舒血管反应均减弱( P < 0.05)。结论　钙化血管僵硬度增加,舒缩功能均明显降低。     

Nω-硝基-L-精氨酸甲酯对失重大鼠肺动脉反应性的影响

目的探讨Nω-硝基-L-精氨酸甲酯(L-NAME)对失重大鼠肺动脉反应性的影响。方法将16只雄性Wistar大鼠按随机数字表法分为对照组和尾悬吊组,每组8只。利用离体血管环灌流技术测量大鼠肺动脉环对苯肾上腺素(PE)的收缩反应和对乙酰胆碱(Ach)的舒张反应,以及L-NAME预处理后动脉环对PE的收缩反应。同时用硝酸还原酶法测定肺动脉组织一氧化氮(NO)含量。结果尾悬吊14d后大鼠肺动脉环对1×10-5~1×10-7mol/L浓度PE的收缩反应均显著下降(P均<0.01);对1×10-6~1×10-8mol/LAch的舒张反应均显著增强(P均<0.05);一氧化氮合酶(NOS)抑制剂L-NAME预处理后动脉环对PE的收缩反应恢复,与对照组比较差异均无显著性。肺动脉组织NO含量增加,两组差异有显著性(P<0.05)。结论模拟失重引起肺动脉血管内皮细胞释放NO增加可能是导致其收缩反应性下降的原因之一。     

The role of calcium desensitization in vascular hyporeactivity and its regulation after hemorrhagic shock in the rat

The objectives of the present study were to investigate the role of calcium desensitization in vascular hyporeactivity, and the regulatory effects of Rho-kinase, protein kinase C (PKC), and protein kinase G (PKG) on calcium sensitivity. The vascular reactivity and calcium sensitivity with superior mesenteric artery (SMA) from hemorrhagic shock rat were observed by measuring the contraction initiated by norepinephrine (NE) and Ca2+ under depolarizing conditions (120 mmol/L K) in an isolated organ perfusion system. Angiotensin II (Ang-II) and Fasudil, the Rho-kinase agonist and inhibitor, phorbol 12-myristate 13-acetate (PMA) and staurosporine, the PKC agonist and inhibitor, 8Br-cGMP and KT-5823, the PKG agonist and inhibitor, and Calyculin A, myosin light chain phosphatase (MLCP) inhibitor were used as tool agents. The results indicated that vascular reactivity and calcium sensitivity were decreased after hemorrhagic shock. The cumulative dose-response curve of SMA to NE and Ca2+ after shock was shifted to the right. Ang-II (10 mol/L) could improve the decreased vascular reactivity by increasing the calcium sensitivity of SMA, and insulin (100 nmol/L) could further decrease the vascular reactivity by decreasing the calcium sensitivity of SMA. These results suggested that the vasculature after shock was desensitized to calcium, which played an important role in the onset of vascular hyporeactivity after shock. PMA and KT-5823 could increase the sensitivity of SMA to Ca2+ and made the cumulative dose-response curve shift to the left. In contrast, Fasudil, staurosporine, and 8Br-cGMP decreased the sensitivity of SMA to Ca2+ and made the cumulative dose-response curve of Ca2+ shift to the right. Calyculin A (10 mol/L) pretreatment further enhanced Ang-II, and PMA induced increase of calcium sensitivity, yet weakened the 8Br-cGMP-induced decrease of calcium sensitivity. Taken together, the data suggest that Rho-kinase, PKC, and PKG are involved in the regulation of calcium sensitivity of vascular smooth muscle after hemorrhagic shock, and their regulatory effects on calcium sensitivity of vasculature are possibly related to MLCP.     

Changes of Rho kinase activity after hemorrhagic shock and its role in shock-induced biphasic response of vascular reactivity and calcium sensitivity

The purpose of the present study is to investigate the changes of Rho kinase activity and its role in biphasic response of vascular reactivity and calcium sensitivity after hemorrhagic shock. The vascular reactivity and calcium sensitivity of superior mesenteric artery (SMA) from hemorrhagic shock rats were determined via observing the contraction initiated by norepinephrine (NE) and Ca under depolarizing conditions (120 mmol/L K) with isolated organ perfusion system. At same time, Rho kinase activity in mesenteric artery was measured, and the effects of Rho kinase activity-regulating agents, angiotensin II (Ang-II), insulin, and Y-27632, on vascular reactivity and calcium sensitivity were also observed. The results indicated that the vascular reactivity and calcium sensitivity were increased at early shock (immediate and 30 min after shock) and decreased at late shock (1 and 2 h after shock). The maximal contractions of NE and Ca were significantly increased (P < 0.05 or P < 0.01) at early shock. But they were significantly decreased at late shock (P < 0.05 or P < 0.01). Rho kinase activity was significantly increased at early shock (immediate after shock) (P < 0.05) but significantly decreased at 1 and 2 h after shock (P < 0.05 or P < 0.01). It was positively correlated with the changes of vascular reactivity and calcium sensitivity. Insulin decreased the increased contractile response of SMA to NE and Caat early shock (P < 0.05 or P < 0.01). Angiotensin II increased the decreased contractile response of SMA to NE and Ca at 2-h shock (P < 0.05 or P < 0.01); Y-27632, Rho kinase-specific antagonist, decreased the contractile response of SMA to NE and Ca at 2-h shock, and abolished Ang-II induced the increase of vascular reactivity and calcium sensitivity. The results suggest that Rho kinase may be involved in the biphasic change of vascular reactivity and calcium sensitivity after hemorrhagic shock. Rho kinase may regulate vascular reactivity through the regulation of calcium sensitivity. Rho kinase-regulating agents may have some beneficial effects on shock-induced vascular hyporeactivity.     

预处理对失血性休克大鼠肠系膜上动脉收缩反应性的影响

目的评价不同条件预处理对失血性休克血管功能的保护作用机制。方法采用大鼠失血性休克模型，观察不同条件预处理（失血预处理及吡哪地尔预处理）对由激动剂[去甲肾上腺素（NE）]诱导在体大鼠肠系膜上动脉（SMA）收缩反应性的影响。结果5％～10％失血预处理对休克大鼠存活率无显著改善，而吡哪地尔可明显改善休克后120min的大鼠存活率。5％失血预处理30min可上调大鼠休克后0min使用NE前后的股动脉压变化，而预处理24h可降低大鼠休克前股动脉压变化，但对休克后使用NE前后的股动脉压变化无明显影响；吡哪地尔预处理1h可降低大鼠休克前使用NE前后的股动脉压变化，而预处理24h对大鼠休克后的股动脉压变化均无影响。5％失血预处理24h可改善休克后120min大鼠SMA对NE的收缩反应性，使用NE后的管径变化显著增加（P〈0．01）；吡哪地尔预处理1h和24h可明显降低大鼠休克前SMA对NE的收缩反应性，使用NE后的管径变化显著降低（P均〈0．05），但吡哪地尔预处理（1h和24h）均可改善休克后120min大鼠SMA对NE的收缩反应性，使用NE后的管径变化显著增加（P均〈0．05）；而格列苯脲可部分取消吡哪地尔的这一作用。结论吡哪地尔预处理24h可降低休克前大鼠SMA对NE的收缩反应性，并可改善休克后120min大鼠SMA对NE的收缩反应性，且使休克大鼠存活率明显提高。吡哪地尔预处理24h对失血性休克大鼠血管功能的保护作用可能与ATP敏感性钾通道有关。     

Mechanisms of Rho kinase regulation of vascular reactivity following hemorrhagic shock in rats

Our previous research showed that Rho kinase took part in the regulation of vascular hyporeactivity after shock. The objective of the present study was to investigate its mechanism. With isolated superior mesenteric artery (SMA) from hemorrhagic shock rats, we studied the relationship of Rho kinase regulating vascular reactivity to calcium sensitivity and myosin light chain phosphatase (MLCP) and myosin light chain kinase (MLCK). The vascular reactivity and calcium sensitivity of SMA were observed by measuring the contraction initiated by accumulative norepinephrine (NE) and calcium under depolarizing condition (120 mM K(+)) with an isolated organ perfusion system. Hypoxia-treated vascular smooth muscle cells (VSMCs) were used to study the effects of Rho kinase on the activity of MLCP and MLCK and the phosphorylation of 20-kDa myosin light chain (MLC(20)). Myosin light chain (20 kDa) phosphorylation of VSMC in mesenteric artery was detected by immunoprecipitation and Western blotting. The activity of MLCP and MLCK was assayed by enzymatic catalysis. The contractile response of VSMC was measured by the ratio of accumulative infiltration of fluorescent isothiocyanate-conjugated bovine serum albumin through transwell. The results indicated that the vascular reactivity and calcium sensitivity of SMA to NE and calcium following hemorrhagic shock and the contractile response of VSMC to NE following hypoxia were significantly decreased. Angiotensin II (Ang-II), the Rho kinase stimulator, significantly improved hypoxia or hemorrhagic shock-induced decrease of vascular reactivity and calcium sensitivity. These effects of Ang-II on vascular reactivity were abolished by Y-27632, the specific Rho kinase inhibitor. Calyculin A, the MLCP inhibitor, further enhanced Ang-II-induced increase of calcium sensitivity, but ML-9, the MLCK inhibitor, had no effect. Further studies showed Ang-II reversed the hypoxia-induced increase of MLCP activity and increased the hypoxia-induced decrease of MLC(20) phosphorylation in VSMC. It was suggested that Rho kinase played an important role in the regulation of vascular reactivity after hemorrhagic shock. The mechanisms may be related to its calcium sensitivity regulation. Rho kinase up-regulates calcium sensitivity of VSMC possibly through inhibiting the activity of MLCP and increasing the phosphorylation of MLC(20).     

聚腺苷二磷酸核糖基聚合酶在大鼠失血性休克后血管低反应性发生中的作用

目的 研究聚腺苷二磷酸核糖基聚合酶(PARP)在大鼠失血性休克后血管低反应性发生中的作用.方法 将SD大鼠随机分为休克组、PARP抑制剂3-氨基苯甲酰胺(3-AB)预处理+休克组和假手术对照组,采用股动脉放血复制失血性休克模型.在体观察给予3 μg/kg去甲肾上腺素(NE)升高血压的幅度;离体测定肠系膜上动脉血管环对NE的反应性;硝酸还原酶法测定血浆和肠系膜上动脉血管环组织匀浆中一氧化氮(NO)的含量.结果 休克模型完成后即刻静脉给NE,休克组血压升高幅度显著低于假手术对照组(P＜0.01);回输血1 h后再次静脉给NE,休克组血压显著低于3-AB预处理+休克组和假手术对照组(P＜0.05和P＜0.01).假手术对照组最大收缩张力[(0.367 1±0.221 3)g/mm]＞3-AB预处理+休克组C(0.286 4±0.153 2)g/mm]＞休克组C(0.185 6±0.11 3)g/mm,P＜0.05或P＜0.01];与休克组比较,3-AB预处理+休克组量一效曲线左移,在NE终浓度为10-7、10-6和10-5 mol/L时其收缩力显著增加(P均＜0.05).3组间血浆NO含量差异均无统计学意义,3-AB预处理+休克组血浆和肠系膜上动脉组织匀浆中NO含量虽较休克组稍有降低,但两组问比较差异无统计学意义.结论 PARP参与了大鼠失血性休克后血管低反应性的发生.     

肌内皮缝隙连接对失血性休克大鼠血管收缩反应的影响

目的 研究肌内皮缝隙连接（MEGJ）对失血性休克大鼠内皮依赖性和非依赖性血管收缩反应的影响。方法 56只SD大鼠按随机数字表法分为去甲肾上腺素（NE）组和杨梅黄酮组；NE组分为正常对照以及休克0、0．5、1和2h5个亚组；杨梅黄酮组分为正常对照以及休克0、0．5、1、2、3和4h7个亚组。各组取其肠系膜上动脉（SMA）制成血管环，分别测量在18α-甘草次酸（18α-GA）作用前后血管环对NE和杨梅黄酮反应性的变化。结果 SMA血管环对NE的反应性表现为：休克0h和0．5h组明显高于正常对照组和其他休克时间点组，休克1h和2h组明显低于正常对照组和休克0h和0．5h组；18α-GA对NE诱导的SMA血管环收缩反应性无明显影响。SMA血管环对杨梅黄酮的反应主要表现为：休克0、0．5、1和2h组明显高于正常对照组，于休克2h达最高点；休克3h和4h组明显低于正常对照组，运用18α-GA阻断MEGJ后，各组血管环的收缩反应性较18α-GA作用前明显下降，其中以休克1、2和3h组下降幅度明显大于其他组。结论 失血性休克后早期，内皮依赖和非依赖性的血管收缩反应均有不同程度代偿性增加，休克1h和2h表现为非内皮依赖性血管收缩反应下降，休克3h和4h表现为内皮依赖性血管收缩反应明显降低；MEGJ在休克后内皮依赖性血管收缩反应的变化中起重要调节作用。