内皮源舒张因子合成抑制剂致大鼠心血管变化及意义

目的：探讨内皮源舒张因子（ＥＤＲＦ）合成受抑制时的心血管病理生理的变化及意义。方法：实验组大鼠（ｎ＝６）长期应用ＥＤＲＦ抑制剂──Ｌ－硝基精氨酸１５ｍｇ，ｋｇ~（－１）／ｄ，腹腔注射，共２８天），对照组（ｎ＝６）给予注射用水。结果：与对照组比较，Ｌ－硝基精氨酸使大鼠血压明显增高、心率减慢、心功能增强，主动脉环对去甲肾上腺素（１０~（１１）～１０~（－５）ｍｏｌ／Ｌ）和内皮素（１０~（－１０）～１０~（－６）ｍｏｌ／Ｌ）的收缩反应增强（Ｐ＜０．０５），对乙酰胆碱（１０~（－９）～１０~（－５）ｍｏｌ／Ｌ）和降钙素基因相关肽（１０~（－１０）～１０~（－８）ｍｏｌ／Ｌ）舒张反应减弱（Ｐ均＜０．０５），血浆和组织内皮素增高，主动脉组织环磷酸鸟苷活性减低，血浆血管紧张素Ⅱ和肾素活性减低，血浆丙二醛增高。肾入球小动脉内膜增厚。结论：ＥＤＲＦ对心血管有重要调控功能，ＥＤＲＦ减少可导致心血管一系列病理生理变化。     

一氧化氮对缺氧性肺动脉高压大鼠血浆降钙素基因相关肽？…

目的 探讨一氧化氮（ＮＯ）对缺氧性肺动态高压（ＨＰＨ）大鼠血浆降钙素基因相关肽（ＣＧＲＰ）含量的影响。方法 将Ｗｉｓｔａｒ大鼠４０只分为四组：对照组（ｎ＝１０）,缺氧组（ｎ＝１０）,缺氧＋Ｌ－ＮＡＭＥ组（ｎ＝１０）,缺年头＋Ｌ－Ａｒｇ组（ｎ＝１０）。通过Ｐ５０压力传感器测量定四组大鼠肺动脉平均压（ＰＡＭＰ）,缺氧＋Ｌ－Ａｒｇ组的ＰＡＭＰ显著低于缺氧组（Ｐ〈０．０５）;缺氧组的右室（ＲＶ）干重／左室     

8—甲氧基补骨脂素对人离体肺动脉收缩的影响

目的通过观察８－甲氧基补骨脂素（８－ＭＯＰ）对人肺动脉收缩的影响，探讨８－ＭＯＰ舒张肺动脉的作用和机制，为８－ＭＯＰ进一步用于降低肺动脉高压提供客观依据。方法采用离体肺动脉平滑肌收缩的实验方法。结果（１）２×１０－５ｍｏｌ／Ｌ的８－ＭＯＰ可使１０－６ｍｏｌ／Ｌ的去甲肾上腺素（ＮＡ）所致收缩的肺动脉环舒张原张力的８８％，其中７例无血管内皮者舒张８３％，４例内皮细胞完好者舒张９７％；（２）经２×１０－５ｍｏｌ／Ｌ的８－ＭＯＰ预处理肺动脉环后，１０－６ｍｏｌ／Ｌ的ＮＡ收缩肺动脉环张力被抑制８９％；（３）上述浓度的８－ＭＯＰ可使ＮＡ收缩肺动脉环的累积量－效曲线不平行右移，最大收缩反应被抑制５５％，抑制参数ＰＤ′２为４．７９。结论提示８－ＭＯＰ有理想的舒张人肺动脉作用，其作用可不依赖于肺动脉内皮细胞的存在，８－ＭＯＰ有可能会成为一种有效降低肺动脉高压药物。     

青藤碱对豚鼠心室肌细胞膜钾离子通道的阻滞作用

利用膜片钳全细胞记录技术研究青藤碱（Ｓｉｎ）对分离的豚鼠单个心室肌细胞膜内向整流钾电流（Ｉｋ１）和延迟整流钾电流（ＩＫ）的影响，发现１μｍｏｌ／Ｌ和５μｍｏｌ／Ｌ的Ｓｉｎ使ＩＫｍａｘ（去极化终末最大ＩＫ）从３５５．９±２１．９ｐＡ分别降至３１７．６±２０．１ｐＡ和２３３．１±１８．７ｐＡ（ｎ＝７，Ｐ均＜０．０５），分别降低了１０．８％和３４．４％；外向尾电流从１５５．１±９．３ｐＡ分别降至１２９．４±６．２ｐＡ和９１．８±６．９ｐＡ（ｎ＝７，Ｐ均＜０．０５），分别降低了１６．６％和４０．８％。当维持电压－４０ｍＶ，超极化－１００ｍＶ时，１μｍｏｌ／Ｌ和５μｍｏｌ／Ｌ的Ｓｉｎ使Ｉｋ１从３．１５７±０．７９４ｎＡ分别降至２．７３５±０．７９９ｎＡ和２．４１１±０．５８１ｎＡ（ｎ＝８，Ｐ均＜０．０１），抑制率分别为１３．４％和２３．６％。５μｍｏｌ／ＬＳｉｎ于不同膜电位水平均能抑制Ｉｋ１，且使Ｉｋ１Ｉ－Ｖ曲线零电位从－８０ｍＶ降至－７０ｍＶ。结果表明Ｓｉｎ对ＩＫ和Ｉｋ１均具浓度依赖性阻滞作用，其延长心肌细胞的复极效应可能与钾通道阻滞有关。     

风湿性心脏病合并重度肺动脉高压患者体外循环前、后肺血流动力学改变

目的：观察风湿性心脏病（风心病）重度肺动脉高压患者体外循环（ＣＰＢ）前、后肺血流动力学变化规律。方法：体外循环前、后用Ｓｗａｎ－Ｇａｎｚ导管监测１５例风心病重度肺动脉高压患者肺血流动力学参数。结果：ＣＰＢ前肺动脉压为３．７／２．３～１１．６／６．０ｋＰａ（２８／１７～８７／４５ｍｍＨｇ），ＣＰＢ后为２．９／１．１～１１．８／５．５ｋＰａ（２２／８～８９／４１ｍｍＨｇ）。二尖瓣替换术后肺动脉收缩压无明显降低（－９％，Ｐ＞０．０５），肺动脉舒张压（－２０％）和平均压（－１４％）均明显降低（Ｐ＜０．０５）。肺血管阻力（ＰＶＲ）在ＣＰＢ前高达６０．３±４０．９ｋＰａ·ｓ／Ｌ，ＣＰＢ后明显降低（－４０％，Ｐ＜０．０５）。回归方程为：ＣＰＢ后ＰＶＲ＝０．５４６ＰＶＲｂ＋２３．２４，Ｒ２＝０．６５１（ＰＶＲｂ为肺血管阻力基础值）。鱼精蛋白静脉用药１０例，肺动脉压升高者４例；动脉用药５例，均未发现肺动脉压改变。结论：风心病肺动脉高压患者术后大部分ＰＶＲ不能恢复正常。动脉系统用药可减少肝素鱼精蛋白复合物引起的不良反应。     

门脉高压大鼠门静脉及周围血NO水平观察

目的了解门脉高压鼠血清一氧化氮（ＮＯ）含量变化及意义．方法以部分门静脉结扎大鼠为模型（ｎ＝１２），在部分门静脉结扎及假手术组大鼠（ｎ＝８）术后２周取门静脉血和周围静脉血，采用荧光分析法测量ＮＯ－２含量反应ＮＯ水平．结果门脉高压组门静脉血ＮＯ－２为０７６６μｍｏｌ／Ｌ±００９７μｍｏｌ／Ｌ，周围静脉血为０６８７μｍｏｌ／Ｌ±００９２μｍｏｌ／Ｌ，两者比较相差显著（Ｐ＜００１）；对照组门脉血ＮＯ－２为０６１３μｍｏｌ／Ｌ±００８４μｍｏｌ／Ｌ，周围血为０５９１μｍｏｌ／Ｌ±００４５μｍｏｌ／Ｌ，二者无明显区别（Ｐ＞００５）．门脉高压组与对照组比较，门脉血和外周血中ＮＯ－２含量均显著高于对照组（Ｐ＜００１）．结论门脉高压大鼠血清ＮＯ－２浓度升高，尤以门静脉血含量升高显著，表明门脉高压大鼠血中ＮＯ生成增多，可能在门脉高压症发病中具有一定作用．     

关附甲素对单个心室肌细胞钠通道电流的频率依赖性和使用依赖性阻滞作用

用膜片钳全细胞法研究关附甲素（ＧＡ）对单个心室肌细胞钠通道电流（ＩＮａ）的频率依赖性和使用依赖性影响。结果：４０μｍｏｌ／ＬＧＡ在刺激频率０．５，１．０，２．０Ｈｚ时使ＩＮａ峰值由用药前的７．９３±２．３ｎＡ分别降至４．８１±１．３，３．２３±１．１和１．２８±０．８ｎＡ（ｎ＝８，Ｐ均＜０．０５），抑制率分别是３９．３％、５９．３％和８３．９％。在脉冲串刺激时，维持电位－９０ｍＶ、指令电位－３０ｍＶ，灌流前ＩＮａ为７．６９±１．３３ｎＡ；４０μｍｏｌ／ＬＧＡ灌流后第１，１０，２０，３０个脉冲ＩＮａ分别是４．２４±０．９８，３．２５±０．７４，２．３３±０．６４和２．０６±０．７０ｎＡ（ｎ＝６，Ｐ均＜０．０１）；而在维持电位－８０ｍＶ，指令电位－３０ｍＶ时，ＧＡ灌流前ＩＮａ为７．５１±１．４３ｎＡ，在灌流后第１，１０，２０，３０个脉冲分别是４．１９±１．０９，２．２８±０．４１，１．２７±０．２４和０．８９±０．２５ｎＡ（ｎ＝６，Ｐ均＜０．０１）。提示：ＧＡ抑制ＩＮａ具有频率依赖性及使用依赖性，其频率依赖性和使用依赖性的机理相同。     

蛋白激酶C激活剂对缺氧性动脉高压大鼠离体肺动脉环反应性？…

观察缺氧性动脉高压大鼠离体肺动脉环对蛋白激酶激活剂豆蔻酸佛波酰乙酰的反应性变化。方法取缺氧２周并已经形成肺动脉高压的大鼠和正常对照组大鼠肺动脉环,观察在离体情况下对０．５μｍｏｌ／ＬＰＭＡ的最大张力反应及达到二分之一最大张力所需的时间,并描绘两肺动脉环对０．０１－１０．０μｍｏｌ／ＬＰＭＡ的浓度－反应曲线。     

周围血单个核细胞抑制胰岛素释放的实验研究

将新发病的ＩＤＤＭ病人周围血单个核细胞（ＰＢＭＣ）同大鼠胰岛共同培养２０个小时后用Ｌ－精氨酸刺激，收集并测定基础和刺激后培养上清中胰岛素的含量，结果显示：ＩＤＤＭ病人ＰＢＭＣ作用下的基础胰岛素释放（１１７．９±１４．０±μＵ·１０ｉｓｌｅｔｓ－１／２０ｈ）（ｎ＝１１）和刺激后胰岛素释放（１４７．５±３２．３μＵ·１０ｉｓｌｅｔｓ－１／３ｈ）（ｎ＝１１），显著低于正常人ＰＢＭＣ作用下的基础胰岛素释放（１８４．８±２９．５μＵ）（ｎ＝１０，Ｐ＜０．０１）和刺激后胰岛素释放（１９５．０±２７．４μＵ）（ｎ＝１０，Ｐ＜０．０１）。结果表明新发病的ＩＤＤＭ病人ＰＢＭＣ能够抑制大鼠胰岛基础和刺激后胰岛素的释放。     

钙通道阻滞剂及L—精氨酸对肺动脉高压的影响

采用常压间竭低氧模型，观察了钙通道拮抗剂尼群地平（Ｎｉｔ）、硝苯吡啶（Ｎｉｆ）、内皮依赖性血管舒张因子（ＥＤＲＦ）合成前体Ｌ－精氨酸（Ｌ－Ａ）对大鼠慢性低氧性肺动脉高压的预防作用。结果提示：三者均能预防低氧性肺动脉高压形成和减轻低氧引起的右室肥大：Ｎｉｔ、Ｎｉｆ与Ｌ－Ａ比较无显著性差异（Ｐ＞０．０５）；Ｎｉｔ对低氧性肺动脉高压的降压作用较Ｎｉｆ稍好。     

电压门控钾通道在慢性缺氧性肺动脉高压发展中的作用

目的:探究慢性缺氧对肺动脉平滑肌细胞电压门控钾通道（Kv）的影响及其在慢性缺氧性肺动脉高压发生发展中的作用。方法:50只雄性SD大鼠随机分为常氧对照组（10只）和慢性缺氧5 d、10 d、20 d及30 d组（各10只）。慢性缺氧组大鼠每天在低氧仓中予以缺氧8 h,分别取缺氧5 d、10 d、20 d及30 d的大鼠进行实验。测量平均肺动脉压（mPAP）并应用全细胞膜片钳技术记录肺动脉平滑肌细胞电压门控钾通道电流（IK）。结果:慢性缺氧显著减低大鼠肺动脉平滑肌细胞的IK峰值及I V曲线漂移。慢性缺氧5 d组肺动脉平滑肌细胞的IK密度及I V曲线与常氧组均没有显著差异;而慢性缺氧10 d组肺动脉平滑肌细胞的IK密度及I V曲线与常氧组均有显著差异(P< 0.05),随着缺氧时间的延长,IK密度的峰值进一步降低。与常氧组相比较,慢性缺氧10 d组大鼠的mPAP明显增加(P<0.05),随着缺氧时间的增加,mPAP进一步增加;mPAP的增加与IK密度的下降呈负相关(r=-0.89769,P<0.01)。结论:慢性缺氧在引发肺动脉高压的过程中伴随有肺动脉平滑肌细胞Kv通道的活性降低,提示Kv参与了肺动脉高压的发生发展。     

低氧性肺动脉高压形成中气体信号分子硫化氢对一氧化碳/血红素加氧酶途径的影响

目的研究新型气体信号分子硫化氢(H2S)在大鼠低氧性肺动脉高压形成中对一氧化碳(CO)/血红素加氧酶(HO1)体系的调节作用,以深入探讨H2S在大鼠低氧性肺动脉高压形成中的病理生理意义。方法将27只大鼠随机分为4组对照组(7只),低氧组(7只),低氧 硫氢化钠(NaHS)组(7只),低氧 炔丙基甘氨酸(PPG)组(6只)。低氧21d后分别测定肺动脉平均压、血浆H2S及CO含量,观察肺动脉平滑肌HO1蛋白及HO1mRNA表达。结果随着低氧性肺动脉高压的形成,血浆H2S的含量显著下降,低氧组[(196±22)μmol/L]与对照组[(294±26)μmol/L]比较差异有显著性(P<005);而CO含量、大、中、小各级肺动脉平滑肌HO1蛋白表达[对照组、低氧组分别为(0313±0020)μmol/L、(0348±0021)μmol/L,066±008、079±008,064±005、077±008,054±005、076±009]及其mRNA表达(对照组、低氧组分别为0573±0148、0813±0052,0532±0131、0831±0043,0473±0102、0819±0032)显著升高(P均<005);外源性给予H2S的供体后,低氧 NaHS组血浆H2S含量[(324±33)μmol/L]显著高于低氧组[(196±22)μmol/L,P<005],肺动脉压显著下降(P<005),且血浆CO含量[(0393±0032)μmol/L]、大、中、小各级肺动脉平滑肌HO1蛋白表达(088±004、089±005、089±006)及mRNA表达(0913±0022、0     

L-精氨酸对低氧性肺动脉高压大鼠肺动脉平滑肌细胞凋亡的影响

目的 探讨L-精氨酸(L-Arg)对低氧性肺动脉高压大鼠不同节段肺动脉平滑肌细胞凋亡的影响。方法 将Wistar大鼠(n=19)随机分为对照组(n=7)、低氧组(n=6)及低氧 L-Arg组(n=6)。经右心导管法测定各组大鼠肺动脉压力和右室(RV)/左室 室间隔(LV S)比值,以分光光度法间接测定血浆一氧化氮(NO)含量,通过TUNEL法检测各组大鼠不同节段的肺动脉平滑肌细胞凋亡数目,并计算肺动脉平滑肌细胞凋亡数目与肺动脉平滑肌细胞数目比值。结果 低氧组大鼠肺动脉平均压(PAMP)显著高于对照组[(2.71±0.29)kPa vs(2.05±0.14)kPa,P<0.01],低氧 L-Arg组大鼠的PAMP显著低于低氧组[(2.23±0.18)kPa vs(2.71±0.29)kPa,P<0.05];低氧组大鼠RV/(LV S)比值显著高于对照组[(0.42±0.03)kPa vs(0.30±0.05)kPa,P<0.01],低氧 L-Arg组大鼠RV/(LV S)比值显著低于低氧组[(0.36±0.02)kPa vs(0.42±0.03)kPa,P<0.01];低氧组大鼠血浆NO含量明显低于对照组[(3.54±0.47)μmol/L vs(4.79±0.17)μmol/L,P<0.05],低氧 L-Arg组大鼠血浆NO含量显著高于低氧组[(5.21±0.26)μmol/L vs(3.54±0.47)μmol/L,P<0.01];低氧组大鼠与终末细支气管伴行的肺动脉和与呼吸细支气管伴行的肺动脉平滑肌细胞凋亡数目与平滑肌细胞数目比值明显低于对照组[(0.051±0.016     

Downregulation of endothelial nitric oxide synthase in rat aorta after prolonged hypoxia in vivo

The goal of this study was to determine whether hypoxia alters expression of endothelial nitric oxide synthase (eNOS) in the systemic circulation. Rats breathed either air or 10% oxygen for 12 hours, 48 hours, or 7 days. Thoracic aortas were excised and either mounted in organ bath myographs or frozen in liquid nitrogen for later extraction of protein and RNA. eNOS protein (Western blotting) was decreased (20% of normoxic control) after 12 hours, 48 hours, and 7 days of hypoxia. eNOS mRNA (ribonuclease protection assay) was similarly reduced. Acetylcholine (10(-4) mol/L) reversed phenylephrine (10(-5) mol/L) preconstriction by 53.3+/-5.6% in aortic rings from normoxic rats and 26.1+/-4.8% in rings from rats exposed to hypoxia for 48 hours (P<0.05), with comparable impairment of relaxation by the calcium ionophore A23187 (10(-5) mol/L). Responses to diethylamine nitric oxide and 8-bromo-cGMP were unaffected. Aortic cGMP levels after incubation with acetylcholine (10(-6) mol/L) averaged 14.0+/-1.8 fmol/mg in rings from normoxic rats compared with 8.7+/-1.0 fmol/mg in rings from hypoxic rats (P<0. 05). Similarly, nitrate concentration (by capillary electrophoresis) in the media in which the rings were incubated was reduced in the hypoxic group (5.6+/-0.23 micromol/L for hypoxic rats and 7.8+/-0.7 micromol/L for normoxic rats). Impaired endothelial NO release may handicap the vascular responses that defend vital organ function during hypoxia.     

Prolonged nitric oxide inhalation fails to regress hypoxic vascular remodeling in rat lung

STUDY OBJECTIVE: The purpose of present study was to investigate whether long-term nitric oxide (NO) inhalation during the recovery in air might improve the regression of chronic hypoxic pulmonary hypertension (PH) and vascular changes. MATERIALS AND METHODS: The rats were exposed to 10 ppm of NO in air for 10 days (n = 12) and 30 days (n = 4), or 40 ppm of NO in air for 10 days (n = 6) and 30 days (n = 12) following 10 days of hypobaric hypoxia (380 mm Hg, 10% oxygen). For each NO group, air control rats following hypoxic exposure were studied at the same time (n = 13, 11, 9, and 11, respectively). Normal air rats (n = 6) without hypoxic exposure and rats (n = 7) following 10 days of hypoxic exposure were used as normal and chronic hypoxic control groups, respectively. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. An additional 16 rats were used to investigate the recovery of pulmonary artery pressure with (n = 8) and without NO inhalation (n = 8) after 10 days of hypobaric hypoxia. RESULTS: Long-term hypoxia-induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes, each of which regressed partly after recovery in room air. There were no differences among rats with and without NO during each recovery period in RVH, medial wall thickness of muscular artery, and the percentages of muscularized arteries at the alveolar wall and duct levels. Continuous inhaled 40 ppm NO decreased pulmonary artery pressure from 40.1 +/- 1.1 to 29.9 +/- 3.8 mm Hg (mean +/- SE) [n = 8], which was not different in the rats without NO inhalation (n = 8). Urine nitrate level was higher in rats that had inhaled NO. CONCLUSION: Continuous NO inhalation showed no effect on regression of pulmonary vascular remodeling in chronic hypoxic PH after returning to room air.     

Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease

OBJECTIVE: The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured. RESULTS: Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 +/- 1.11 ng/dL (H) and 4.35 +/- 1.62 (C) at 4 weeks with a p value < 0.005 and FT4 of 2.01 +/- 0.36 (H) and 3.25 +/- 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 +/- 0.9 ng/mL (H) vs. 3.11 +/- 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 +/- 14.8 ng/mL (H) and 114.1 +/- 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 +/- 18.1 (C) and 92.7 +/- 10.3 (C) and 4 and 8 weeks with p < 0.0005 and < 0.05 respectively. Growth hormone levels were lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively. CONCLUSION: Chronic hypoxia in our neonatal rat model was associated with decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to centrally mediated.     

Altered mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries of hypertensive versus normotensive Dahl rats

OBJECTIVE: To determine mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries from normotensive (NT) and hypertensive (HT) Dahl salt-sensitive (SS) rats. METHODS: Isolated gracilis arteries (GA) from both rat groups were viewed via television microscopy and vascular responses to a reduction in PO2 from 145 mm Hg to 40 mm Hg were measured with a video micrometer. Responses were determined following endothelium removal and following inhibition of specific biochemical pathways regulating vascular tone. RESULTS: Hypoxic dilation was impaired in HT rats versus NT controls. Endothelium removal abolished hypoxic dilation in NT rats, although a significant dilation to hypoxia remained in vessels from HT animals. Inhibition of cytochrome P450 (CP450) 4A enzymes blunted hypoxic dilation in both groups, while inhibition of epoxyeicosatrienoic acid (EET) production impaired responses in NT rats only. Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) production or blockade of membrane receptors for 20-HETE reduced hypoxic dilation in HT rats, with minimal effects in NT animals. Nitric oxide synthase inhibition had no effect on hypoxic dilation in either group, while cyclooxygenase inhibition significantly reduced this response in both groups. CONCLUSIONS: These results suggest that the mechanisms of hypoxic dilation in GA from NT Dahl-SS rats are altered with HT, impairing the response to reduced PO2. While hypoxia induces substantial prostanoid release in both groups, the role of CP450 4A enzymes is shifted from EET production in NT rats toward inhibition of 20-HETE production in HT rats.     

Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice.

Nitric oxide and prostaglandins were shown to contribute to the endothelial mediation of flow-induced dilation of skeletal muscle arterioles of rats. Thus, we hypothesized that flow-induced dilation and its mediation are altered in gracilis muscle arterioles of mice deficient in the gene for endothelial nitric oxide synthase (eNOS-KO) compared with control wild-type (WT) mice. Gracilis muscle arterioles ( approximately 80 micrometer) of male mice were isolated, then cannulated and pressurized in a vessel chamber. The increases in diameter elicited by increases in perfusate flow from 0 to 10 microq/min were similar in arterioles from eNOS-KO (n=28) and WT (n=22) mice ( approximately 20 micrometer at 10 microL/min flow). Removal of the endothelium eliminated flow-induced dilations in vessels of both strains of mice. N(omega)-nitro-L-arginine (L-NNA, 10(-4) mol/L) significantly inhibited flow-induced dilation in arterioles of WT mice by approximately 51% but had no effect on responses of arterioles from eNOS-KO mice. Indomethacin (INDO, 10(-5) mol/L) inhibited flow-induced dilation of WT mice by approximately 49%, whereas it completely abolished this response in arterioles of eNOS-KO mice. Simultaneous administration of INDO and L-NNA eliminated flow-induced responses in arterioles of WT mice. Dilations to carbaprostacyclin were similar at concentrations of 10(-8) and 3x10(-8) mol/L but decreased significantly at 10(-7) mol/L in arterioles of eNOS-KO compared with those of WT mice. These findings demonstrate that, despite the lack of nitric oxide mediation, flow-induced dilation is close to normal in arterioles of eNOS-KO mice because of an enhanced release of endothelial dilator prostaglandins and suggest that this vascular adaptation may contribute to the regulation of peripheral resistance in eNOS-KO mice.     

内皮舒张因子在缺氧肺动脉收缩中的作用

本工作在离体灌流肺动脉环模型及培养的牛肺动脉内皮细胞探讨内皮舒张因子 (EDRF/NO)在缺氧肺动脉收缩中的作用。结果发现 ,在内皮完整血管环加入NO合成抑制剂L NNA(10 -4mol/L)、NO合成前体L Arg(10 -2 mol/L)分别升高 ( 80 % ,P <0 .0 1)和降低 (-35 % ,P <0 .0 5 )缺氧肺动脉收缩幅度 ;给予硝酸甘油 (10 -4 mol/L)直接补充NO可降低缺氧肺动脉收缩幅度 ,此效应可被可溶性鸟苷酸环化酶抑制剂亚甲蓝部分逆转 ;用Northern印渍杂交技术显示缺氧使培养的牛肺动脉内皮细胞NO合成酶(NOS)基因表达明显受抑。结果提示缺氧时NOS基因表达受抑及NO合成释放降低可能是缺氧肺动脉收缩的发生机制之一。