L—精氨酸二肽对大鼠异丙肾上腺素心肌损伤的影响

在大鼠异丙肾上腺素心肌坏死模型上发现心肌环－磷酸岛苷含量明显减少，冠脉流量降低，冠血管对乙酰胆碱扩血管反应减弱，而对硝普钠的扩血管反应（非内皮依赖性）无明显改变。用内皮衍生松驰因子前体Ｌ－精氨酸二肽治疗可明显减轻ＩＳＯ心肌损伤，增加心肌ｃＧＭＰ含量，增加冠脉灌流量，改善冠血管对Ａｃｈ的舒张反应。实验结果表明，ＩＳＯ心肌坏死时冠脉内皮ＥＤＲＦ生成减少，应用Ｌ－精氨酸二肽具有防治意义。     

内皮舒张因子对大鼠颈动脉血栓形成的影响

在ＦｅＣｌ３损伤血管内皮导致的大鼠颈动脉血栓形成模型上发现血栓段血管组织环磷鸟苷（ｃＧＭＰ）含量减少，其内皮依赖性的乙酰胆碱（Ａｃｈ）扩血管作用减弱，而对非内皮依赖性的硝普钠扩血管反应无明显改变，病理形态观察可见动脉血栓形成和血管内皮严重损伤。用一氧化氮合成酶抑制剂ＬＮＮＡ处理后的动物明显地促进血栓形成，该作用可被一氧化氮前体Ｌ－精氨酸（Ｌ－Ａｒｇ）所拮抗，用Ｌ－Ａｒｇ处理后的动物显著减轻血栓形成     

缺氧—再给氧对大鼠胸主动脉环内皮依赖血管舒张反应的影响

生物测定法观察大鼠胸主动脉环经缺氧－再给氧、机械去内皮后，血管内皮分泌内皮细胞舒张因子（ＥＤＲＦ）的能力，ＥＤＲＦ前体Ｌ－精氨酸（Ｌ－Ａｒｇ）及拮抗剂ＮＧ－甲基－Ｌ－精氨酸（Ｌ－ＮＭＭＡ）对大鼠胸主动脉内皮ＥＤＲＦ合成和分泌的影响。发现缺氧－再给氧及去内皮的血管环对乙酰胆碱（Ａｃｈ）的舒张反应明显减弱或丧失，而对硝酸甘油的舒张反应仍保存。Ｌ－Ａｒｇ可加强正常内皮环和缺氧－再给氧环对Ａｃｈ的舒张反应     

维生素D3引起大鼠血管钙超载对血管L-精氨酸/NO途径的影响

目的：观察血管钙超载对Ｌ－精氨酸／ＮＯ途径的影响。方法：维生素Ｄ３（ＶｉｔＤ３）注射引起大鼠血管钙超载,检测血管ＮＯ生成、ｃＧＭＰ含量、Ｌ－瓜氨酸转化及Ｌ－精氨酸转运的变化,并与口服Ｌ－精氨酸治疗组大鼠比较。结果：大鼠血管钙含量（９４４±１８８）ｖｓ对照（１０７±１８）μｍｏｌ／ｇ干重,（Ｐ＜００１）,血管ＮＯ生成减少,组织ｃＧＭＰ含量降低,但Ｌ－瓜氨酸转化增高,Ｌ－精氨酸（Ｌ－Ａｒｇ）高和低亲和性转运的最大速率（Ｖｍａｘ）分别降低５０５％和４５８％（Ｐ＜００１）。口服Ｌ－Ａｒｇ治疗的大鼠血管ＮＯ生成和ｃＧＭＰ含量都较钙超载大鼠明显增高（Ｐ＜００１）,Ｌ－Ａｒｇ高、低亲和性转运的Ｖｍａｘ增加。结论：血管钙超载对Ｌ－Ａｒｇ／ＮＯ途径损伤的主要环节在Ｌ－Ａｒｇ的跨膜转运,补充ＮＯ前体Ｌ－Ａｒｇ可能减轻钙超载引起的血管损伤。     

缺氧－再给氧对大鼠胸主动脉环内皮依赖血管舒张反应的影响

生物测定法观察大鼠胸主动脉环经缺氧－再给氧、机械去内皮后，血管内皮分泌内皮细胞舒张因子（ＥＤＲＦ）的能力，ＥＤＲＦ前体Ｌ－精氨酸（Ｌ－Ａｒｇ）及拮抗剂ＮＧ－甲基－Ｌ－精氨酸（Ｌ－ＮＭＭＡ）对大鼠胸主动脉内皮ＥＤＲＦ合成和分泌的影响。发现缺氧－再给氧及去内皮的血管环对乙酰胆碱（Ａｃｈ）的舒张反应明显减弱或丧失，而对硝酸甘油的舒张反应仍保存。Ｌ－Ａｒｇ可加强正常内皮环和缺氧－再给氧环对Ａｃｈ的舒张反应；Ｌ－ＮＭＭＡ则使该作用消失。Ｌ－ＮＭＭＡ和去内皮均使血管环丧失对Ａｃｈ的舒张反应。提示缺氧－再给氧和去内皮分别可使大鼠胸主动脉内皮分泌ＥＤＲＦ机制受损或丧失，提供外源性Ｌ－Ａｒｇ有促使正常内皮和受损内皮合成和释放ＥＤＲＦ的作用。     

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     

NO－样舒血管因子在大鼠腹膜炎败血症中的作用

为探讨ＮＯ样舒血管因子（ＮＯ－ＬＲＦ）在腹膜炎败血症中的作用及其病理生理意义，本工作在大鼠腹膜炎败血症模型上，发现早、晚期败血症大鼠的离体主动脉环对去甲肾上腺素的反应降低；血管组织ｃＧＭＰ含量增加，表明败血症动物Ｌ－Ａｒｇ／ＮＯ途经增强，用ＮＯ合成前体Ｌ－精氨酸（Ｌ－Ａｒｇ）或ＮＯ合成抑制剂ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ（Ｌ－ＮＮＡ）、可溶性鸟苷酸环化酶抑制剂亚甲蓝灌流，分别增加或降低败血症动物主动脉的上述变化，但上述药物的作用不依赖于血管内皮的存在，提示败血症动物主要为非内皮源性ＮＯ－ＬＲＦ增强。整体实验发现：Ｌ－Ａｒｇ可明显改善而Ｌ－ＮＮＡ却恶化休克过程，提示ＮＯ－ＬＲＦ可能参与败血症休克时机体的适应性保护机制。     

NO—样舒血管因子在大鼠腹膜炎败血症中的作用

为探讨ＮＯ样舒血管因子（ＮＯ－ＬＲＦ）在腹膜炎败血症中的作用及其病理生理意义，本工作在大鼠腹膜炎败血症模型上，发现早、晚期败血症大鼠的离体主动脉环对去甲肾上腺素的反应降低；血管组织ｃＧＭＰ含量增加，表明败血症动物Ｌ－Ａｒｇ／ＮＯ途经增强，用ＮＯ合成前体Ｌ－精氨酸（Ｌ－Ａｒｇ）或ＮＯ合成抑制剂ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ（Ｌ－ＮＮＡ）、可溶性鸟苷酸环化酶抑制剂亚甲蓝灌流，分别增加或降低败血     

L—精氨酸对高脂血症大鼠内皮素分沁的影响

Ｌ－精氨酸对高脂血症大鼠内皮素分沁的影响皖南医学院弋矶山医院（芜湖市２４１００１）王安才王春雷俞国华杨尚印在大鼠高脂血症实验中，Ｌ－精氨酸（Ｌ－ａｒｇｉｎｉｎｅ，Ｌ－Ａｒｇ）于逆转一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ，ＮＯ）减少的同时，对血管内皮分泌内皮...     

L—精氨酸对猪冠状动脉内皮功能的影响

以氧化低密度脂蛋白（ｏｘｉｄｉｚｅｄｌｏｗ－ｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎ，ｏｘ－ＬＤＬ）诱导猪冠状动脉内皮功能障碍，观察Ｌ－精氨酸（Ｌ－ａｒｇｉｎｉｎｅ，Ｌ－ａｒｇ）对正常及内皮功能障碍的冠脉的影响。结果显示ｏｘ－ＬＤＬ可使猪冠脉舒张功能下降而Ｌ－ａｒｇ可部分阻止这一作用。用逆转录ＰＣＲ技术检测了冠脉血管灌流后结构型一氧化氮合成酶（ｃｏｎｓｔｉｔｕｔｉｖｅｎｉｔｒｉｅｃｏｘｉｄｅｓｙｎｔｈａｓｅ，ｃＮＯＳ）ｍＲＮＡ表达，结果表明ｏｘ－ＬＤＬ可抑制血管ｃＮＯＳｍＲＮＡ表达而Ｌ－ａｒｇ可拮抗这一抑制作用。     

乙酰胆碱和组织胺对豚鼠离体气管条张力的影响及机制分析

用自制的多个“工”形相连的豚鼠气管条,观察乙酰胆碱、组织胺和异丙基肾上腺素对肌张力的影响,探讨钙激活钾(KC_a)通道功能的变化。结果显示:1.乙酰胆碱和组织胺共同作用时,平滑肌张力升高幅度大于乙酰胆碱和组织胺单独作用,小于两者单独作用之和。2.异丙基肾上腺素引起乙酰胆碱或组织胺所致平滑肌张力下降,甚至低于基础张力,乙酰胆碱和组织胺共同作用时,异丙基肾上腺素也可解痉。结果提示:中等浓度乙酰胆碱和组织胺对增加气管平滑肌张力有协同作用。异丙基肾上腺素引起乙酰胆碱或组织胺所致平滑肌张力下降,表明乙酰胆碱和组织胺引起气管平滑肌痉挛时,KC_a通道处于关闭或大部分关闭状态。     

Arterial size determines the enhancement of contractile responses after suppression of endothelium-derived relaxing factor formation

We studied the effect of endothelium-derived relaxing factor (EDRF) on norepinephrine-induced contractile responses and on the tissue guanosine-3,5-phosphate (cGMP) concentration of isolated rabbit arteries with an increasing endothelium to smooth muscle cell ratio (aorta, femoral and mesenteric arteries). After suppression of EDRF formation (either by N ^G-nitro-l-arginine or, in mesenteric arteries, by saponin), contractions elicited by cumulative doses of norepinephrine were unaltered in aorta but were enhanced by 22.5% in femoral arteries and by 44.3% in mesenteric arteries (at the highest norepinephrine concentration). The cGMP concentration (pmol/mg protein) of unstimulated, endotheliumintact vessels decreased after suppression of EDRF formation from 1.09±0.24 to 0.74±0.28 in aortic, from 2.86±0.4 to 0.61±0.19 in femoral and from 6.3±0.9 to 0.7±0.15 in mesenteric arterial segments. The basal cGMP concentration did not differ in endothelium-denuded segments of these arteries, suggesting a similar basal activity of soluble guanylate cyclase (sGC). A higher sensitivity of sGC may have contributed to the higher cGMP concentration observed in the smaller arteries, since in the presence of sodium nitroprusside the cGMP concentration of endothelium-denuded segments increased 1.8-fold in aortic, 2.9-fold in femoral and 2.4 fold in mesenteric arterial segments. However, these differences in sGC activation cannot be solely responsible for the high basal cGMP concentration in endotheliumintact mesenteric arteries. The greater ratio of endothelium to smooth muscle cell layers in the smaller arteries might result in a higher EDRF concentration in the vascular wall and subsequently in a higher cGMP concentration. In conclusion, these data support the view of a greater importance of EDRF-mediated vascular control in small arteries than in large conduit arteries.     

脂质体携载L—精氨酸对离体大鼠心脏缺血—再灌注损伤的保护作用

本工作在离体灌流的大鼠心脏缺血-再灌注(I/R)损伤模型上,观察了脂质体携载L-精氨酸(L-Arg)的保护作用。结果发现,1mol/L L-Arg脂质体灌流心脏,明显抑制缺血心脏再灌注时心肌MDA含量和线粒体Ca~(2+)含量的增加,显著减少心肌细胞内的酶(乳酸脱氢酶、组织强白酶D)和肌红蛋白的漏出及心肌MDA的释放,明显增加冠脉流量。而相同剂量的游离L-Arg则无明显保护效应。我们在离体大鼠灌流的主动脉条上进一步发现,L-Arg脂质体具有显著的血管舒张效应。而游离L-Arg则不具有明显舒张效应。结果表明,脂质体作为药物载体,包裹内源性EDRF释放剂防治心肌I/R损伤是有效的。可能具有临床应用前景。     

Effect of Vasodilating Drugs on External Carotid and Pulpal Blood Flow in Dogs: “Stealing” of Dental Perfusion Pressure

Blood flow in the external carotid artery (ECBF) and dental pulp (PBF) was measured during arterial infusion of vasodilators (isoprenaline, papaverine, acetylcholine and bradykinin). Systemic arterial pressure (AP) and local arterial pressure of the teeth (LAP) were recorded in a femoral and the lateral nasal artery respectively. All four vasodilators were found to increase ECBF and simultaneously reduce lateral nasal arterial pressure—or in other words—to “steal” perfusion pressure from the teeth. AP remained practically unchanged whereas PBF was variably affected. During infusion of isoprenaline PBF decreased on average by 19% of control. Papaverine nearly doubled PBF, while bradykinin caused no consistent change. Great pulpal flow variations were often recorded during constant acetylcholine infusion rate. The variable effect of the four vasodilators on PBF could partly be explained by the fall in LAP. Calculated pulpal resistance (LAP/PBF) showed no consistent change during isoprenaline infusion, bradykinin caused a slight fall and papaverine reduced LAP/PBF by 49%. The experiments demonstrate that due to the “stealing” of dental perfusion pressure caused by vasodilation in the neighbouring tissues, the effect of vasodilators on pulpal resistance vessels cannot be estimated without knowledge of the pressure in the small arteries directly feeding the teeth.     

Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: "stealing" of dental perfusion pressure.

Blood flow in the external cartoid artery (ECBF) and dental pulp (PBF) was measured during arterial infusion of vasodilators (isoprenaline, papaverine, acetylcholine and bradykinin). Systemic arterial pressure (AP) and local arterial pressure of the teeth (LAP) were recorded in a femoral and the lateral nasal artery respectively. All four vasodilators were found to increase ECBF and simultaneously reduce lateral nasal arterial pressure--or in other words-to STEAL" PERFUSION PRESSURE FROM THE TEETH. AP remained practically unchanged whereas PBF was variably affected. During infusion of isoprenaline PBF decreased on average by 19% of control. Papaverine nearly doubled PBG, while bradykinin caused no consistent change. Great pulpal flow variations were often recorded during constant acetylcholine infusion rate. The variable effect of the four vasodilators on PBF could partly be explained by the fall in LAP. Calculated pulpal resistance (LAP/PBF) showed no consistent change during isoprenaline infusion, bradykinin caused a slight fall and papaverine reduced LAP/PBF by 49%. The experiments demonstrate that due to the "stealing" of dental perfusion pressure caused by vasodilation in the neighbouring tissues, the effect of vasodilators on pulpal resistance vessels cannot be estimated without knowledge of the pressure in the small arteries directly feeding the teeth.     

兔肺动脉高压时肺组织中内皮素和鸟苷环－磷酸含量的变化及意义

１１只兔进行从降主动脉至左肺动脉的分流手术，观察三个月后形成了左侧肺动脉高压。取左、右肺组织测定内皮素（ＥＴ）和ｃＧＭＰ，发现左侧肺组织中ＥＴ含量较右侧为高，而ｃＧＭＰ则较右侧为低，两侧比较差异显著。因组织中ｃＧＭＰ的含量间接反映了内皮舒缩血管因子（ＥＤＲＦ）的含量，故认为肺高压时肺组织中ＥＴ分泌增加和ＥＤＲＦ分泌减少。两者的变化在肺高压的形成过程中可能起重要作用。     

N G-nitro-l-arginine antagonizes endothelium-dependent dilator responses by inhibiting endothelium-derived relaxing factor release in the isolated rabbit heart

The effects of a recently described inhibitor of endothelial NO synthesis, N ^G-nitro-l-arginine (l-NNA), on the vasomotor responses to endothelium-dependent and independent vasodilators, and on the release of endothelium-derived relaxing factor (EDRF), were studied in the isolated saline-perfused rabbit heart. Infusion of l-NNA (30 M) resulted in a 52±12% increase in basal coronary perfusion pressure. The vasomotor responses to 1 M acetylcholine (ACh) and serotonin after l-NNA became biphasic, showing a small transient dilation followed by a pronounced vasoconstriction. In contrast, the dilation observed with sodium nitroprusside was not affected by l-NNA. None of the above-mentioned effects was elicited by the Stereo-isomer d-NNA. Similarly, an increase in the basal coronary perfusion pressure by endothelin-1 (0.3 nM) to the same level as observed with l-NNA did not alter the vasomotor responses to ACh and sodium nitroprusside. The increase in cyclic GMP (cGMP) in platelets passing through the coronary vascular bed was used as an index of EDRF release. Platelet cGMP amounted to 0.50±0.10 pmol/mg protein after passage through the coronary bed of the unstimulated heart. When platelets were injected during an ACh infusion (1 M), a 2.7 fold increase in cGMP was observed (P<0.01). After a 30-min infusion with l-NNA, the cGMP content of platelets passing through the unstimulated heart was reduced by 62%. Likewise, the ACh-induced increase in platelet cGMP was totally blocked. These results show that l-NNA inhibits EDRF release, and is thus a potent and selective inhibitor of EDRF-mediated dilation in the isolated rabbit heart.     

The response of isolated rat heart cells to cardiotoxic concentrations of isoprenaline

Isolated beating rat heart myocytes were incubated with the sympathomimetic amine isoprenaline at concentrations which are known to induce myocardial necrosis in vivo. Incubation with isoprenaline did not induce changes in cell morphology nor impair the ability of the cells to take up and retain fluorescein diacetate. These results suggest that myocardial cells are not the main target in isoprenaline-induced necrosis and that some alternate indirect mechanism must be involved.