自发性高血压大鼠主动脉血管功能的变化

目的探讨自发性高血压大鼠(SHR)血管舒缩功能变化及其可能机制.方法以32周龄SHR大鼠(n=7)为研究对象,年龄、性别配对的WKY(n=7)大鼠作对照组.观察离体胸主动脉环对不同血管活性物质的舒缩反应.结果 SHR主动脉环对乙酰胆碱(ACh)诱导的内皮依赖性舒张反应明显减弱;对ACh的内皮依赖性收缩反应明显高于WKY.L-NAME加强ACh的收缩作用;对硝普钠(SNP)的收缩反应在两组间无差别.结论 SHR大鼠存在内皮功能障碍,表现为内皮依赖性舒张作用减弱,其机制与内皮合成NO减少及内皮依赖性收缩作用增强有关.     

女贞子、淫羊藿补肾中药对自发性高血压大鼠主动脉内皮舒缩功能的影响

目的 研究补肾中药女贞子、淫羊藿对自发性高血压大鼠(SHR)的血压、主动脉内皮舒张因子一氧化氮(NO)及收缩因子内皮素(ET-1)的影响,探讨补肾中药调节主动脉内皮舒缩功能的可能机制.方法 采用随机对照研究的方法将40只12~14周龄自发性高血压大鼠(SHR)随机分为女贞子组、淫羊藿组、阳性对照组、模型组,以同龄同种系正常血压的京都种大鼠(Wistar-Kyoto rat,WKY)10只作为正常组;女贞子组、淫羊藿组、阳性对照组分别给予女贞子、淫羊藿水煎液,依那普利水溶液,模型组和正常组给予蒸馏水灌胃.2 w后采用多导生理记录仪检测大鼠血压,处死大鼠后取腹主动脉血测定血清一氧化氮(NO),血浆内皮素-1(ET-1)的含量,取主动脉检测内皮eNOS、ET-1蛋白及eNOS mRNA、ET-1mRNA的表达.结果 用药后女贞子、淫羊藿使SHR大鼠的血压有所降低,但差异无统计学意义;女贞子组、淫羊藿组血液NO、主动脉内皮eNOS蛋白及eNOS mRNA表达较模型组升高(P<0.05),血液ET、主动脉内皮ET-1蛋白及ET-1 mRNA表达均明显降低(P<0.05).结论 单味中药女贞子、淫羊藿虽然没有明显降低血压,但略有下降的趋势,且能调节主动脉血管内皮舒缩因子.     

肾血管性高血压大鼠血管内皮细胞功能的变化

目的观察肾血管性高血压(RVH)大鼠血管内皮细胞功能的变化并探讨其机制。方法体重为160~180g健康雄性Wistar大鼠随机分成2组高血压模型(RVH)组及对照(C)组。术后4周,用颈动脉直接插管法测定大鼠血压,应用生物测定法观察大鼠离体主动脉舒缩反应及美蓝(MB)、L-NAME、硝普钠(SNP)、左旋精氨酸(L-Arg)对其的影响。结果RVH大鼠离体胸主动脉环对苯肾上腺素(PHE)引起的收缩反应比对照组明显增高,去除内皮后可消除两组差异。鸟苷酸环化酶抑制剂美蓝及NO合成酶抑制剂L-NAME可使对照组收缩反应增加较RVH组明显。RVH大鼠胸主动脉环由乙酰胆碱(Ach)引起的内皮依赖性舒张反应较对照组明显减弱,而对非内皮依赖性松弛剂硝普钠(SNP)的舒张反应两组间无显著差异。NO合成底物L-Arg能显著提高RVH大鼠内皮依赖性舒张反应。结论肾血管性高血压血管内皮依赖的收缩反应增强,舒张反应减弱。其机制是血管内皮产生和释放EDRF(NO)功能受损和(或)EDRF作用减弱,合成NO的底物L-Arg不足。     

肾血管性高血压大鼠血管内皮细胞功能的变化

目的观察肾血管性高血压(RVH)大鼠血管内皮细胞功能的变化并探讨其机制.方法体重为160～180 g健康雄性Wistar大鼠随机分成2组:高血压模型(RVH)组及对照(C)组.术后4周,用颈动脉直接插管法测定大鼠血压,应用生物测定法观察大鼠离体主动脉舒缩反应及美蓝(MB)、L-NAME、硝普钠(SNP)、左旋精氨酸(L-Arg)对其的影响.结果 RVH大鼠离体胸主动脉环对苯肾上腺素(PHE)引起的收缩反应比对照组明显增高,去除内皮后可消除两组差异.鸟苷酸环化酶抑制剂美蓝及NO合成酶抑制剂L-NAME可使对照组收缩反应增加较RVH组明显.RVH大鼠胸主动脉环由乙酰胆碱(Ach)引起的内皮依赖性舒张反应较对照组明显减弱,而对非内皮依赖性松弛剂硝普钠(SNP)的舒张反应两组间无显著差异.NO合成底物L-Arg能显著提高RVH大鼠内皮依赖性舒张反应.结论肾血管性高血压血管内皮依赖的收缩反应增强,舒张反应减弱.其机制是血管内皮产生和释放EDRF(NO)功能受损和(或)EDRF作用减弱,合成NO的底物L-Arg不足.     

苯那普利对自发性高血压大鼠血管内皮舒张功能的改善作用

目的 :探讨苯那普利能否改善自发性高血压大鼠 (SHR)血管内皮舒张功能。　　方法 :采用体外灌注法测定苯那普利治疗组 (治疗组 )及对照组胸主动脉环对乙酰胆碱的舒张反应 ,并比较两组血清中 NO3- 浓度、动脉组织中环鸟苷酸 (c GMP)水平。　　结果 :与对照组比较 ,治疗组胸主动脉环对乙酰胆碱的最大舒张反应明显增强 (P<0 .0 1)。左旋硝基精氨酸 (L-NNA)几乎完全消除了治疗组和对照组舒张反应之间的差异。治疗组血清 NO3-浓度和动脉组织 c GMP的含量均明显增加 (P均 <0 .0 1)。　　结论 :苯那普利长期治疗可明显改善 SHR血管内皮舒张功能 ,其机制可能是增加了内皮一氧化氮的合成或释放     

幼龄自发性高血压大鼠血管内皮功能研究

目的　本研究选取幼龄自发性高血压大鼠(SHR)作为研究对象 ,观察其尚未出现高血压时血浆一氧化氮 (NO)、血管壁一氧化氮合酶 (NOS)的情况及负荷运动对它的影响 ,从而进一步了解内皮功能在遗传性高血压发病中的地位。方法　 5～ 6wSHR、WKY各 2 8只随机分为静态组、运动组 ,静态组行有创血压测定、血浆NO及血管壁NOS测定 ,运动组行游泳负荷运动后行上述指标测定 ,分别比较静态组WKY、SHR 6min内的平均血压、峰血压、达峰时间、血浆NO的均数和运动组WHY、SHR的上述指标的均数 ,比较各组NOS免疫组化染色。结果　 (1)静态组WKY、SHR6min内的平均血压、峰血压、达峰时间有显著差异 (P <0 0 5 ) ;运动组WKY、SHR的平均血压、峰血压、达峰时间没有显著差异 (P >0 .0 5 ) ;(2 )静态组WKY、SHR的血浆NO无显著差异 (P <0 .0 5 ) ,运动组WKY、SHR的NO有显著差异(P <0 .0 5 ) ;无论是SHR还是SKY ,其运动组血浆NO均高于静态组 ,但WKY鼠运动组比静态组增高更明显 ;(3)各组血管壁NOS免疫组化染色范围未见明显不同。结论　SHR在高血压期前已存在内皮舒血管储备功能的不足。推测内皮舒血管功能的障碍可能参与了遗传性高血压的发病。     

一氧化氮对自发性高血压大鼠血管内皮功能的作用

目的　探讨自发性高血压大鼠 (SHR)内皮舒张功能不全的发生机制。方法　采用体外灌注的方法测定大鼠胸主动脉环对不同浓度乙酰胆碱的舒张反应变化 ,并测定血清中NO-3浓度和动脉组织中环鸟苷酸水平。结果　与魏 凯二氏大鼠 (WKY)比较 ,SHR胸主动脉环对乙酰胆碱的舒张反应明显减弱。左旋硝基精氨酸 (L NNA)可明显抑制大鼠胸主动脉环对乙酰胆碱的舒张反应 ,但并不能消除SHR和WKY对乙酰胆碱舒张反应之间的差异。与WKY比较 ,SHR血中NO-3水平明显降低 (P<0 .0 1) ,动脉组织中环鸟苷酸含量降低 (P<0 .0 1)。结论　SHR内皮依赖的血管舒张功能减低 ;一氧化氮 (NO)的生成或释放不足可能直接参与了SHR血管内皮依赖的舒张功能不全。     

心房利钠因子对自发性高血压大鼠主动脉条血管反应性的影响

自发性高血压大鼠(包括卒中易感型)的胸主动脉条对心房利钠因子-(103-126)的舒张作用的敏感性显著降低,提示可能与高血压的发病有关。初步探讨了它的发生机制。     

血管内皮功能不全与高血压

血管内皮细胞可以通过合成和释放多种血管活性物质，对血管张力发挥重要的局部调节作用，从而影响外周阻力和血压。本文综述了近年关于内皮源性舒张因子（EDRF）及内皮源收缩因子（EDCF），高血压内皮功能不全及其可能机制和药物能否改善血管内皮功能的研究。     

左旋氨氯地平对自发性高血压大鼠内皮功能的保护作用

目的 探讨左旋氨氯地平对自发性高血压大鼠(SHR)内皮依赖性舒张功能的影响.方法 20只SHR随机分为左旋氨氯地平治疗组(SHR-A组)和高血压对照组(SHR-C组),同周龄WKY大鼠作为正常对照组(WKY组).左旋氨氯地平治疗12周后,检测各组大鼠胸主动脉对乙酰胆碱(ACh)和硝普钠(SNP)的舒张反应,以及血清NO、内皮素(ET)和超氧化物歧化酶(SOD)的水平.结果 与SHR-C组相比,SHR-A组胸主动脉环对ACh的最大舒张反应明显增强(P<0.01).左旋硝基精氨酸甲酯能够消除两组之间的差异.3组大鼠胸主动脉环对SNP的最大舒张反应无统计学意义(P>0.05).SHR-A组与SHR-C组、WKY组比较血清NO、SOD浓度明显增加,而血浆ET水平显著降低(P<0.05).结论 左旋氨氯地平干预能够显著改善SHR血管内皮依赖性舒张功能,其作用机制可能与增加内皮NO的合成和释放有关.     

Contractions to Endothelin in Normotensive and Spontaneously Hypertensive Rats: Role of Endothelium and Prostaglandins

Contractions to endothelin-1 in aortas of the spontaneously hypertensive rats (SHR) were compared with those of normotensive controls (WKY); rings with and without endothelium were studied in organ chambers. Contractions to endothelin were smaller in aortas of SHR compared to WKY, whether the endothelium was present or not. The presence of a functional endothelium reduced contractions to the peptide in both strains. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to nitric oxide were observed in rings from both strains during contraction with endothelin. Indomethacin reduced the contractions to endothelin in the aorta from SHR with endothelium, but not in those without endothelium; it did not significantly affect endothelin-induced contractions in rings of WKY with or without endothelium. These experiments demonstrate that contractions of the vascular smooth muscle to endothelin are reduced in the aorta of the SHR. The basal and stimulated release of endothelium-derived relaxing factor inhibits contractions to endothelin in the aorta from both strains. The inhibitor of cyclooxygenase indomethacin does not prevent the response of the vascular smooth muscle to endothelin; however, endothelin may stimulate the release of an indomethacin-sensitive endothelium-derived contracting factor in the SHR aorta.     

Basal Endothelium-Derived Relaxing Factor in the Thoracic Aorta of Spontaneously Hypertensive Rats and Wistar-Kyoto Rats

利用卒中型自发性高血压大鼠（SHRsp）与正常血压对照Wistar－Kyoto大鼠（WKY）的胸主动脉螺旋条，研究了基础EDRF对α1激动剂本肾上腺素（PE）引起的血管收缩的影响。结果发现：（1）不论在SHRsp还是WKY，血管内皮的存在明显抑制PE引起的血管收缩，表现为收缩幅度减小，EC50加大。（2）不论是去内皮条还是有内皮条，其收组反应在SHRsp与WKY间无显著差异。（3）在WKY，10－5mol／L，10－4mol／L的左旋硝基精氨酸（L－NNA，一氧化氮合成酶抑制剂）或3．3×10－4mol／L的还原型血红蛋白（HbO2，EDRF灭活剂）均可使有内皮条的收缩达到去内皮条的水平。（4）在SHRsp，10－5mol／L的L－NNA与3．3×10－6mol／LHbO2虽增强有皮条的收缩，但并不能使其达到去皮条的水平。10－4mol／L的L－NNA也只能使有内皮条的收缩幅度达到去皮条的水平。本实验结果表明：（1）血管内皮细胞释放的基础EDRF调节α1激动剂引起的收缩反应。基础EDRF的作用可被内皮细胞NO合成酶的抑制剂或EDRF的清除剂所阻断，（2）在SHRsp，L－NNA与HbO2对PE引起的血管收缩的增强作用比在WKY弱，提示高血压时基础EDRF产生或作用的机制可能发生改变，由正常时完全依赖NO合成酶变为部分地不依赖NO合成酶。推测其原因为高血压时一种非NO性质的基础EDRF     

黄嘌呤氧化酶对血管内皮功能障碍的影响

目的考察黄嘌呤氧化酶(xanthine oxidase)在自发性高血压大鼠(SHR)血管舒缩及内皮功能障碍中的作用。方法采用尾套法测定SHR和正常大鼠(WKY)血压;Greiss反应测定血清一氧化氮分泌量;FRAP(ferric reduction abilitypower)法测定主动脉蛋白总抗氧化能力;RT-PCR法考察黄嘌呤氧化酶及内皮型一氧化氮合酶(eNOS)mRNA表达情况;血管环舒缩测定来评价黄嘌呤氧化酶抑制剂别嘌呤醇(oxypurinol,Oxy)对大鼠腹主动脉内皮依赖性舒张反应的影响。结果SHR血压(191.1±5.6)显著高于WKY大鼠(140.4±5.9)mmHg;SHR血清NO分泌量(28.4±5.4)、主动脉蛋白总抗氧化能力(1.02±0.14)U/μg蛋白和腹主动脉内皮依赖性舒张反应(66.2±4.6)%均显著低于WKY[分别为(51.6±5.8),(2.8±0.3)U/μgpro和81.0%±2.7%);而心、肾及主动脉中黄嘌呤氧化酶表达均显著高于WKY大鼠(P<0.05)。黄嘌呤氧化酶抑制剂Oxy能明显降低黄嘌呤氧化酶mRNA表达(降低31.6%),且改善腹主动脉内皮依赖型舒张反应(提高20.2%),但对eNOS表达则无显著影响。结论结果提示SHR中存在内皮功能障碍和氧化应激状态,黄嘌呤氧化酶参与了SHR内皮功能障碍。     

黄嘌呤氧化酶对血管内皮功能障碍的影响

目的 考察黄嘌呤氧化酶(xanthine oxidase)在自发性高血压大鼠(SHR)血管舒缩及内皮功能障碍中的作用.方法 采用尾套法测定SHR和正常大鼠(WKY)血压;Greiss反应测定血清一氧化氮分泌量;FRAP(ferric reduction ability power)法测定主动脉蛋白总抗氧化能力;RT-PCR法考察黄嘌呤氧化酶及内皮型一氧化氮合酶(eNOS)mRNA表达情况;血管环舒缩测定来评价黄嘌呤氧化酶抑制剂别嘌呤醇(oxypurinol,Oxy)对大鼠腹主动脉内皮依赖性舒张反应的影响.结果 SHR血压(191.1±5.6)显著高于WKY大鼠(140.4±5.9)mm Hg;SHR血清NO分泌量(28.4±5.4)、主动脉蛋白总抗氧化能力(1.02±0.14)U/μg蛋白和腹主动脉内皮依赖性舒张反应(66.2±4.6)%均显著低于WKY[分别为(51.6±5.8),(2.8±0.3)U/μg pro和81.0%±2.7%);而心、肾及主动脉中黄嘌呤氧化酶表达均显著高于WKY大鼠(P＜0.05).黄嘌呤氧化酶抑制剂Oxy能明显降低黄嘌呤氧化酶mRNA表达(降低31.6%),且改善腹主动脉内皮依赖型舒张反应(提高20.2%),但对eNOS表达则无显著影响.结论 结果提示SHR中存在内皮功能障碍和氧化应激状态,黄嘌呤氧化酶参与了SHR内皮功能障碍.     

Effect of Nicorandil on Cardiac Dysfunction During Reperfusion in Normotensive and Spontaneously Hypertensive Rats

The cardioprotective effect of nicorandil, an opener of ATP-sensitive potassium channels, was studied in the isolated perfused hearts of the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. Controls received no drug. In the nicorandil group, the hearts were treated with 0.03 to 0.3 mmol/L nicorandil for 15 min before ischemia. Left ventricular developed pressure (LVDP and end diastolic pressure (LVEDP) at 30 min of reperfusion were significantly lower and larger, respectively, in SHR than in WKY rats. Nicorandil improved LVDP and decreased LVEDP at 30 min of reperfusion in both SHR and WKY rats dose-dependently. The hypertensive heart in the early stage is already susceptible to reperfusion-cardiac dysfunction. Nicorandil has a beneficial effect on the post-ischemic dysfunction in both SHR and WKY rats.     

Hypophosphatemia in Infant and Adult Spontaneously Hypertensive Rats

Spontaneously hypertensive rats (SHR) newborn to three months of age exhibit significantly lower serum inorganic phosphate concentrations than do controls from two normotensive strains, Sprague Dawley (CD) and Wistar Kyoto (WKY), During early posnatal development serum inorganic phosphate increases in all strains and plateaus from eight to twelve weeks. This rise in serum phosphate occurs during a period when blood pressure is increasing in normotensive strains as well as in SHR. Hypophosphatemia even in prehypertensive SHR may relate to elevated parathyroid hormone levels in SHR and may explain the salutary effects of high calcium diets in this hypertensive model.     

Alterations in Vasopressin Mechanisms in Captopril-Treated Spontaneously Hypertensive Rats

The effects of lifetime captopril treatment on vasopressin (VP) were assessed in spontaneously hypertensive rats (SHR). Pregnant and nursing dams were treated with oral Captopril (100 mg/kg/day), After weaning, the pups were maintained on Captopril (50/kg/day) for 19–20 wks. Blood pressures of Captopriltreated SHR were in the normotensive range and significantly lower (p<.001) than SHR control rats. Control and Captopril-treated SHR were perfused and brains were sectioned for immunohistochemical staining with a polyclonal antibody directed against vasopressin (VP). Compared to control SHR, Captopril-treated rats displayed decreased VP-like immunoreactivity in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Captopril treatment also selectively decreased the number of brightly labeled cell bodies in the SON and PVN and reduced VP-like labeling in the axons of the neurons in these nuclei. Concurrent with a decrease in VP-like immunoreactivity, Captopril treatment reduced plasma VP levels (RIA) (p<0.01, Captopril, 5.6±0.5 pg/ml; control, 11.8±2.2 pg/ml.). Scatchard analysis of ³H-VP binding indicated that Captopril treatment increased the number but not the affinity of VP receptors in the hypothalamus and brain stem of SHR. These results suggest that in SHR oral Captopril treatment attenuates the synthesis and release of VP, an effect that may contribute to the blood pressure lowering effect of converting, enzyme inhibitors.     

Dietary Magnesium does not Affect Blood Pressure in Spontaneously Hypertensive Rats

To determine the therapeutic effectiveness of dietary magnesium in the treatment of established hypertension, 21 male spontaneously hypertensive rats were fed altered levels of magnesium oxide from 17 to 29 weeks of age. The rats were divided into three groups of approximately equal mean baseline systolic blood pressures and fed AIN 76A purified diets containing magnesium at 0.01% (low), 0.05% (normal), and 0.40% (high) levels. Mean systolic blood pressures in the conscious SHR during the 12 week period and terminal direct blood pressures under anesthesia were not significantly different among treatment groups. Total and ultrafilterable serum magnesium concentrations reflected dietary magnesium intake. Total and ultrafilterable serum calcium levels were significantly higher (p<0.05) in the low magnesium-fed SHR. Histopathologic alterations indicative of aging did not differ among treatment groups. Therefore, in spite of altered serum mineral status, blood pressure and histopathology were not affected by dietary magnesium.