肾血管性高血压大鼠外周血管生成素2的变化及替米沙坦的干预作用

目的:研究血管生成素-2(angiopoietin-2,Ang-2)在肾血管性高血压及心肌肥厚进展中的作用,并探讨替米沙坦对肾血管性高血压、心肌肥厚、心脏功能及外周Ang-2水平的影响。方法:清洁级雄性SD大鼠24只,随机分为对照组、假手术组、两肾一夹(two-kidney one clip,2K1C)组和2K1C+替米沙坦组。2K1C组及2K1C+替米沙坦组采用2K1C方法制备高血压模型,其中2K1C+替米沙坦组每天以替米沙坦10mg/kg灌胃干预,2K1C组采用等量蒸馏水灌胃。分别于术前及术后经动脉插管测血压,8周时以超声心动图检测心脏结构及功能变化,随后处死大鼠,取外周动脉血清以ELISA方法检测Ang-2水平。结果:(1)与对照组、假手术组相比,2K1C组血压显著升高、心肌肥厚明显(P0.01);2K1C+替米沙坦组血压较2K1C组明显降低,心肌肥厚亦明显减轻(P0.01);(2)与对照组、假手术组相比,2K1C组动脉血清Ang-2水平明显升高(P0.01),且与血压水平、心肌肥厚程度呈正相关;2K1C+替米沙坦组Ang-2水平与2K1C组差异无统计学意义(P0.05)。结论:Ang-2在肾血管性高血压外周动脉血清中表达增加,且与心肌肥厚相关;替米沙坦可显著降低肾血管性高血压大鼠的血压、抑制心肌肥厚,对外周血清Ang-2水平无明显影响,提示替米沙坦降压机制可能与Ang-2无关。     

替米沙坦对老年高血压患者尿酸和超敏C反应蛋白的影响

目的探讨替米沙坦对老年原发性高血压合并高尿酸血症患者的治疗作用以及对超敏C反应蛋白（hs-CRP）的影响。方法选择66例老年1～2级原发性高血压患者,血尿酸（BUA）420～530μmol／L,随机分成2组：替米沙坦组35例（替米沙坦40-80mg／d）、对照组31例（苯磺酸氨氯地平5～10mg／d）,两组患者用药2周末测血压。治疗12周后观察收缩压、舒张压、空腹BUA、hs-CRP水平。结果治疗2周末两组患者血压开始下降,4周后血压趋于稳定,与治疗前比较差异有统计学意义（P〈0．01）,治疗12周后两组血压比较差异无统计学意义。替米沙坦组治疗12周后BUA、hs—CRP水平较治疗前下降（P〈0．01）,对照组hs—CRP较治疗前下降（P〈0．01）。结论替米沙坦除有良好的降压作用外,尚能有效地降低原发性高血压患者hs—CRP、BUA水平。     

替米沙坦对自发性高血压大鼠心肌ACE2表达的影响

选择16只12周龄雄性自发性高血压大鼠随机分为自发性高血压组（SHR组,n=8）和替米沙坦组（n=8）,替米沙坦组大鼠予以替米沙坦5mg／（kg·d）灌胃,给药时间8周,同时取8只12周龄雄性Wistar大鼠作为对照组,利用免疫组织化学染色和逆转录聚合酶链反应检测各组动物心肌血管紧张素转换酶2（ACE2）的表达。结果发现,与对照组比较,SHR组心肌ACE2表达显著降低（P〈0．05）,与SHR组比较,替米沙坦组经8周治疗后,ACE2表达显著增高（P〈0．05）,替米沙坦组血压、心肌重量指数及心肌胶原容积分数较SHR组均明显下降（P均〈0．05）。认为高血压大鼠心肌ACE2表达降低,替米沙坦能够上调高血压大鼠心肌ACE2的表达,该作用可能为血管紧张素Ⅱ1型受体拮抗剂在高血压病心脏保护作用的新机制。     

Toll样受体在Goldblatt鼠左室心肌中的表达-炎症与左心室肥厚相关的一个证据

目的 观察肾血管性高血压大鼠（2K1C，Goldblatt高血压大鼠）左室心肌中Toll样受体4（Toll-like receptor4，TLR4）、核因子κB（NFκB）的表达情况并探讨其影响因素。方法 采用免疫组化法检测10只雄性Goldblatt高血压大鼠和6只正常雄性Sprague-Dawley（SD）大鼠左室心肌中TLR4、核因子κB的表达情况，维多利亚蓝一丽春红法行心肌胶原染色评价心肌纤维化程度，根据超声心动图评价左室结构和功能。结果 高血压大鼠左室心肌组织中TLR4和NFκB的表达水平升高（P〈0．01），两者呈高度正相关（r=0．824，P〈0．01）；TLR4表达水平与左室心肌纤维化呈正相关；TLR4表达水平与左室心肌肥厚程度、收缩功能指数显著相关。结论 TLR4信号通路的活化可能参与Goldblatt大鼠心肌肥厚的发生和发展。     

替米沙坦对2型糖尿病大鼠心肌超微结构的影响

目的观察替米沙坦对2型糖尿病大鼠心肌的保护作用，探讨其可能的细胞因子机制。方法40只雄性SD大鼠随机分为3组：正常对照组（c组）10只、糖尿病模型组（D组）15只和替米沙坦组（T组）15只。给予替米沙坦，12周末结束实验，免疫组织化学方法检测心肌组织中转化生长因子β1（TGF-β1）和肝细胞生长因子（HGF）蛋白含量，电镜观察左室心肌。结果与C组比较，D组心肌细胞内线粒体数目增多，肌原纤维灶性变性、溶解，肌原纤维间间隙增宽。T组改变明显减轻。与C组比较，D、T组TGF-β1蛋白表达显著升高（47．86±1．35、65．00±1．20与79．00±2．18，P〈0．01），T组TGF-β1蛋白表达显著低于D组（47．86＋1．35与65．00±1．20，P〈0．01）；与C组比较，D、T组HGF蛋白表达显著升高（63．86±3．13、45．00±2．07与78．78±1．72，P〈0．01），T组HGF蛋白表达显著高于D组（45．00±2．07与63．86±3．13，P〈0．01）。结论替米沙坦能够改善糖尿病大鼠心肌超微结构，可能与降低心肌中TGF—β1蛋白，升高HGF蛋白表达有关。     

替米沙坦对压力超负荷左心室肥厚大鼠心肌I型胶原代谢的影响

目的：探讨压力超负荷左心室肥厚大鼠I型胶原代谢特点及替米沙坦的干预效果。方法：24只雄性Spargue—Dawley大鼠随机分为假手术组（n=8）、左心室肥厚组（n=8）和替米沙坦组（n=8）。行腹主动脉缩窄术建立高血压左心室肥厚大鼠模型。各组干预4周后处死大鼠,称其体质量及左心室质量,计算左心室质量指数（LVMI）。将左心室心肌行Masson染剂染色,观察并测量其胶原容积分数（CVr）。用ELISA法检测3组大鼠血清I型前胶原羧基端肽（PICP）及I型胶原羧基端交联肽（ICTP）的浓度,并计算PICP／ICTP的比值,直线相关分析PICP及PICP／IC—TP比值与CVF的相关性。结果：与假手术组相比,左心室肥厚组左心室质量、LVMI、CVF、血清PICP及PICP／ICTP的比值均显著升高（均P〈0．05）;与左心室肥厚组相比,替米沙坦组左心室质量、LVMI、CVF、血清PICP、PICP／ICTP的比值均显著降低（均P〈0．05）。3组问的ICTP相比较,差异无统计学意义;PICP及PICP／ICTP比值均与CVF呈正相关（r值分别为0．830、0．842,均P〈0．01）。结论：压力超负荷左心室肥厚大鼠I型胶原合成增加、降解相对不足,合成与降解的不平衡是造成其左心室心肌间质纤维化的原因之一。替米沙坦可以抑制I型胶原的合成,纠正其合成与降解不平衡,从而有效地抑制及逆转心肌间质纤维化。     

替米沙坦对高血压大鼠血管前纤维蛋白1及ERK磷酸化水平的影响

目的：探讨替米沙坦对自发性高血压大鼠（SHR）血管前纤维蛋白1（Profmn-1）及细胞外信号调节激酶（ERK1／2）磷酸化水平的影响。方法：选取10周龄SHR及其同源对照魏-凯氏（WKY）大鼠,给予替米沙坦（5～10mg／kg·d）或安慰剂,为期10周。尾套法测量大鼠尾血压。采用实时定量聚合酶链式反应（PCR）和Western免疫印迹检测治疗后大鼠主动脉组织中Profilin-1mRNA和蛋白及ERK1／2磷酸化水平。结果：与WKY对照组相比,SHR大鼠血压明显升高[（126±3．5）mmHg：（195±6．1）mmHg],伴血管Profilin—1mRNA[（1．0±0．11）;（7．8±0．57）]及ERK硫酸化水平[（1．0±0．11）：（2．43±0．19）]表达明显升高（P均〈0．01）,而经替米沙坦治疗后SHR大鼠血压明显降低[替米沙坦低剂量组（169±6．2）mmHg,高剂量组（161±4．9）mmHg],伴Profilin-1mRNA[替米沙坦低剂量组（4．45±0．92）,高剂量组（1．95±0．41）]表达及ERK1／2磷酸化水平[替米沙坦低剂量组（1．62±0．20）,高剂量组（1．34±0．09）]明显下调（P均〈0．05）。结论：长期替米沙坦治疗可降低高血压大鼠血压水平,降低血管Profilin-1表达及ERK1／2磷酸化水平,提示替米沙坦对高血压血管重塑具有一定的保护功效。     

异莲心碱防止高血压大鼠左室肥厚的可能机制

背景既往报告异莲心碱是从莲子心中分离的一种双苄基喹啉生物碱单体，具有抗心律失常、Ca^2＋拮抗及阻断α受体作用，对高血压左室肥厚有不同程度的改善。高血压左室肥厚心肌肌浆网钙泵（SERCA）活力较正常心肌降低。目的探讨异莲心碱对高血压大鼠左室肥厚及SERCA活力的影响。方法将二肾一夹肾血管性高血压大鼠（RHR）模型，随机分为3组：正常对照组、肾血管性高血压大鼠对照组（未治疗RHR组）和异莲心碱治疗组。在异莲心碱治疗组持续给药10周后，分别测定各组大鼠的血压、左室质量／体质量，以及左室心肌SERCA活力。结果治疗后，异莲心碱治疗组血压（136．4±14．6）mmHg较未治疗RHR组（189．8±4．4）mmHg显著降低（P〈0．01）；异莲心碱治疗组左室质量／体质量（2．23±0．43）也较未治疗RHR组（2．93±0．52）显著降低（P〈0．05）；异莲心碱治疗组左室心肌SERCA活力[（0．91±0．18）μmol／（gprotein·min）]较未治疗RHR组[（0．61±0．23）μmol／（gprotein·min）]显著升高（P〈0．05），但仍较正常对照组[（1．32±0．18）μmol／（gprotein·min）]低（P〈0．01）。结论异莲心碱能降低RHR的血压，减低RHR的左室质量／体质量，对高血压左室肥厚具有一定的防治作用；其机制可能与异莲心碱能升高RHR肥厚心肌肌浆网SERCA活力，改善心肌细胞内钙超载有关。     

β1受体反义基因治疗对两肾一夹高血压大鼠心肌Bcl-2的影响

目的比较两肾一夹（2K1C）肾性高血压大鼠心肌Bcl-2的表达，探讨阳离子脂质体混合物介导的β1受体反义基因治疗对肾性高血压大鼠血压及心肌Bcl-2表达的影响。方法将18只雄性SD大鼠随机分成3组，每组6只。其中2组12只用来制作两肾一夹高血压模型，作为两肾一夹组；6只作为假手术组，仅分离左肾动脉而不套银夹。两肾一夹模型又分为反义寡核苷酸（β1-AS-ODN）组（反义组）和反向寡核苷酸（InvertedODN，β1-IN—ODN）组（反向组）。阳离子脂质体1，2-bis（oleoyloxy）-3-（trimethylammonio）propane／cholesterol（DOTAP）和辅助脂质体1-a—dioleoylhosp hatidylethanolamine（DOPE）以1：1的摩尔比混合。阳离子脂质体混合物（DOTAP／DOPE）与β1-AS-ODN、β1-IN—ODN混合的摩尔比率均为2．0，经鼠尾静脉注射。监测血压，8周后测定血流动力学指标，免疫组织化学方法检测3组大鼠心肌Bcl-2的表达。结果反义寡核苷酸治疗可使血压显著下降，单剂治疗可维持血压降低27d，血压最大下降39mmHg。反义组的心脏湿重／体重（HW／gw）也显著低于对照组（P〈0．01）。两肾一夹组心肌Bcl-2表达明显高于假手术组，β1-IN—ODN组心肌Bcl-2表达明显高于β1-AS—ODN组。结论以β1受体为靶基因的反义基因对肾性高血压有效，单剂治疗降压持续时间长，而且在抑制血压和左室肥厚的同时也明显抑制心肌Bcl-2的表达，提示β1-AS-ODN对心肌Bcl-2的抑制在抗高血压靶器官损伤过程中起一定的作用。     

替米沙坦对老年原发性高血压患者脂联素的影响

目的探讨替米沙坦对老年原发性高血压患者脂连素的影响。方法老年原发性高血压患者100例,随机分为替米沙坦组与硝苯地平组,各50例,同时选健康体检者100名作为对照,分别测定治疗前后脂联素、空腹血糖、餐后2h血糖、总胆周醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、高敏c反应蛋白。结果原发性高血压患者脂联素水平低于对照组（P〈0．01）。两组治疗组患者血压均下降,替米沙坦组治疗后餐后2h血糖（2hPBG）较治疗前降低,脂联素水平较治疗前升高（P〈0．01）,硝苯地平组脂联素及餐后2h血糖水平治疗前后差异无统计学意义。结论老年高血压患者脂联素水平降低,替米沙坦除降压作用外,能增加脂连素水平和改善糖代谢。     

牛磺酸对肾性高血压大鼠血浆及心肌血管紧张素Ⅱ、醛固酮的影响

目的　观察牛磺酸 (Tau)对肾性高血压大鼠血浆及心肌血管紧张素 (Ang )、醛固酮 (Ald)的影响。方法　Wistar大鼠随机分为假手术组 (Sham组 )、二肾一夹肾性高血压模型组 (2 K1C组 )、Tau治疗组 (2 K1C+Tau组 ) ,每组 8只。测定并比较各组尾动脉收缩压 (SBP)、左心室重量指数 (L VWI)、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 、Ald含量。结果　 2 K1C组大鼠 SBP、L VWI、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 、Ald含量较 Sham组显著增加 (P<0 .0 1)。牛磺酸 (5 0 mg/ kg· d)治疗 8周显著降低 2 K1C大鼠 SBP、L VWI、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 和 Ald含量 (P<0 .0 1)。结论　牛磺酸可降低肾性高血压大鼠循环及心肌局部肾素血管紧张素醛固酮系统 (RAAS)活性 ,抑制心肌细胞肥大及胶原增生 ,有效防治左室肥厚     

不同位置肾素血管紧张素醛固酮系统阻断剂对肾血管性高血压大鼠血浆血管紧张素Ⅱ1型受体及其抗体的影响

目的观察佐芬普利、奥美沙坦、依普利酮对肾性高血压大鼠血压、心肌肥厚及外周血血管紧张素Ⅱ1型受体(AT1R)及其抗体(AT1R-Ab)的影响。方法 120只清洁型雄性SD大鼠随机分为假手术组、两肾一夹组、两肾一夹+佐芬普利组(Z)、两肾一夹+奥美沙坦组(O)和两肾一夹+依普利酮组(E),每组24只。对后4组以两肾一夹制作肾血管性高血压模型。制模4周后,药物干预组分别采用佐芬普利10mg/kg、奥美沙坦3mg/kg、依普利酮100mg/kg灌胃,假手术组、两肾一夹组以等体积蒸馏水灌胃。术后8、12、14周,超声心动图观察心脏结构和功能,每组处死6只大鼠取主动脉血;采用酶联免疫吸附技术(ELISA)检测血浆AT1R、AT1R-Ab水平。结果术后8周,假手术组、两肾一夹组的AT1R水平差异无统计学意义(P>0.05);各干预组AT1R水平较两肾一夹组上升(均P<0.05)。术后12周、14周两肾一夹组大鼠动脉血浆AT1R水平较同期假手术组上调;Z、E干预组AT1R水平较两肾一夹组升高[12周:(74.63±0.83)、(75.85±3.09)比(67.56±1.67)ng/L;14周:(78.29±0.31)、(78.05±1.12)比(73.90±1.98)ng/L,均P<0.05];而O组与两肾一夹组差异无统计学意义(P>0.05)。术后8周,两肾一夹组大鼠血浆AT1R-Ab水平较假手术组升高;术后12、14周两肾一夹组大鼠血浆AT1R-Ab水平较术后8周降低;各时段Z、E组AT1R-Ab水平均较两肾一夹组降低[8周(2.10±0.10)、(2.13±0.18)比(2.75±0.13)ng/L,12周(2.00±0.10)、(2.03±0.1)比(2.32±0.10)ng/L;14周(1.99±0.16)、(2.00±0.09)比(2.23±0.23)ng/L;均P<0.05];而O组与两肾一夹组差异无统计学意义(P>0.05)。结论肾性高血压大鼠血压、血浆AT1R、AT1-Ab水平随时间动态变化。奥美沙坦、佐芬普利、依普利酮降低大鼠血压、减小心肌肥厚程度、上调动脉血AT1R水平;佐芬普利、依普利酮下调动脉血浆AT1R-Ab水平,而奥美沙坦对AT1R-Ab无明显影响。     

Selection criteria for drug-treated animals in two-kidney, one clip renal hypertension

The two-kidney, one clip (2K1C) model of hypertension in the rat does not uniformly result in increased blood pressure. That is, the placement of a clip around one renal artery in a two-kidney rat will usually, but not always, produce hypertension. This is an important problem in studies designed to evaluate the ability of antihypertensive therapy to prevent hypertension. Therefore, an additional objective means other than blood pressure is needed to assess animals that are treated from the outset with antihypertensive therapy. The purpose of this study was to correlate the relative fresh weights of left (clipped)/right (nonclipped) kidneys (LK/RK) with tail-cuff systolic blood pressure in the 2K1C model of renal hypertension and to identify an LK/RK range that would exclude the animals least likely to become hypertensive (failures of the clipping procedure). On a scale of 0.0 to 1.0, an LK/RK ratio of 0.0 was present when the clipped kidney was completely infarcted or atrophied and a ratio of 1.0 was present when the clip did not cause sufficient renal artery stenosis to alter kidney weight. In a series of 72 untreated 2K1C male Sprague-Dawley rats examined 6 to 8 weeks after clipping, 100% of the animals with an LK/RK ratio of 0.5 to 0.8 (n = 19) and 75% with an LK/RK ratio of 0.4 to 0.9 (n = 38) had a blood pressure greater than 150 mm Hg. Less than 50% with an LK/RK ratio below 0.4 or above 0.9 (n = 34) were hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)     

替米沙坦、苯磺酸氨氯地平对大鼠心肌纤维化及血管紧张素-(1-7)的影响

目的:评价替米沙坦(TMST)、苯磺酸氨氯地平(ALDP)对腹主动脉缩窄(AAC)大鼠心肌纤维化的预防作用,了解其血清血管紧张素-(1-7)[Ang-(1-7)]水平的变化.方法:32只8周龄雄性SD大鼠随机对24只施行AAC术,8只施行假手术.术后1周,将施行AAC术的24只大鼠随机分为TMST组[5 mg/(kg·...     

Benidipine inhibits expression of ET-1 and TGF-beta1 in Dahl salt-sensitive hypertensive rats.

Endothelin and growth factors such as transforming growth factor (TGF)-beta1 are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) and TGF-beta1 have been reported in left ventricular hypertrophy, the detailed roles of these substances in hypertrophy remain to be determined. To elucidate the cardioprotective effects of calcium antagonists in left ventricular hypertrophy, we evaluated the effects of long-term treatment with benidipine, a long-acting calcium antagonist, on preproET-1, ET(A) receptor (ETAR) and TGF-beta1 expression in the left ventricle and evaluated the relations between these effects and myocardial remodeling in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. After 5 weeks of feeding an 8% NaCl diet to 6-week-old DS rats (i.e., at 11 weeks of age), a distinct stage of concentric left ventricular hypertrophy (DSLVH) was noted. Benidipine (DSLVH-B group, n= 8; 1 mg/kg/day, subdepressor dose) or vehicle (DSLVH-V group, n=8) was administered to 6-week-old DS rats for 5 weeks, or until the onset of DSLVH stage, and age-matched (11-week-old) Dahl salt-resistant rats fed the same diet served as a control group (DR-C, n=8). Blood pressure was similar between the DSLVH-B and DSLVH-V groups, but was significantly lower in DR-C rats. The preproET-1, ETAR and TGF-beta1 expressions in the left ventricle were significantly higher in DSLVH-V than in DR-C rats, and significantly lower in DSLVH-B than in DSLVH-V. Benidipine administration resulted in significant improvements in the wall-to-lumen ratio and perivascular fibrosis in the coronary arterioles, and in myocardial fibrosis. We therefore concluded that myocardial remodeling and left ventricular hypertrophy in DS hypertensive rats fed a high-salt diet were significantly ameliorated by a subdepressor dose of benidipine, and that this amelioration was partly due to decreases in the expression of ET-1 and TGF-beta1 in the left ventricle.     

Alterations in renal Na+K+ATPase activity and [3H]ouabain binding in Goldblatt hypertensive rabbits

To evaluate the role of renal Na+K+ATPase in the presence of Goldblatt hypertension, the enzyme activity and [3H]ouabain binding were examined in cortical and medullary homogenates from two-kidney, one clip (2K1C), one-kidney, one clip (1K1C), unilaterally nephrectomized and normal rabbits. Four weeks after the surgery, systolic blood pressures (SBPs) of 2K1C and 1K1C rabbits were increased significantly to 128 +/- 3 and 129 +/- 2 mmHg, respectively. In contrast, SBPs in the normal controls and unilateral nephrectomized (1K) animals were 83 +/- 2 and 86 +/- 3 mmHg, respectively. In the 2K1C rabbits, atrophy (91%) occurred in the kidney on the ischaemic side and hypertrophy (110%) occurred in the contralateral kidney. Na+K+ATPase activity and number of [3H]ouabain binding sites were reduced in the homogenates of the ischaemic kidney of 2K1C rabbits. In the 1K1C rabbits, marked hypertrophy of the kidney (155%) occurred, and the activity of Na+K+ATPase and the number of [3H]ouabain binding sites increased slightly in the cortex and medulla, compared with the normal controls. 5'-Nucleotidase, a plasma membrane marker enzyme, remained unchanged in both groups of hypertensive rabbits. Dissociation constant (KD) values for [3H]ouabain binding did not differ significantly in the renal homogenates of of 2K1C and 1K1C, compared with findings in the normal controls. The inhibitory activity of plasma was measured by studying [3H]ouabain binding to Na+K+ATPase of renal tubular basolateral membrane vesicles purified by Percoll gradient. The inhibition was more pronounced with plasma from 2K1C, 1K1C and 1K rabbits than from the control animals. Our findings suggest that in the Goldblatt hypertensive model, changes in Na+K+ATPase activity were due to alterations in glomerular filtration rate (GFR).     

Endothelial nitric oxide synthase protein is reduced in the renal medulla of two-kidney, one-clip hypertensive rats

OBJECTIVE : We studied endothelial nitric oxide synthase (eNOS) expression in the kidneys of two-kidney, one-clip renal hypertensive rats (2K1C) before and after removal of the clip (unclipping, UC). We hypothesised that the haemodynamic changes induced by 2K1C and UC would change eNOS expression in the two kidneys. METHODS : Six weeks after inducing 2K1C, mean arterial pressure (MAP) was measured in conscious rats and hypertension reversed by UC. Left and right kidney eNOS protein in cortex and outer medulla was semi-quantified using immunoblotting. Groups were; normotensive (n = 10), 2K1C (n = 10), 3 h (n = 10), 48 h (n = 7) and 4 weeks (n = 7) after UC. The effect of 7 days of aldosterone or angiotensin II (Ang II) infusion on medullary eNOS protein was tested as well as the effect of L-NAME (nitric oxide (NO) synthase inhibitor) on medullary blood flow (MBF) in anaesthetized 2K1C. RESULTS : UC reduced MAP from 178 +/- 5 to 134 +/- 3 mmHg after 3 h and normalized MAP at 48 h and 4 weeks. The medulla from 2K1C kidneys contained about 33% less eNOS protein compared with normotensive kidneys (P < 0.05). This difference was still evident at 3 h (P < 0.05), but completely reversed at 48 h and 4 weeks after UC. Similar levels of eNOS expression were seen in the left and right kidney at all time points. Cortical eNOS was increased in kidneys from 2K1C. Neither Ang II nor aldosterone affected eNOS expression in the medulla. MBF was under similar influence of NO in 2K1C compared with normotensive kidneys. CONCLUSIONS : 2K1C is associated with reduced levels of eNOS protein in the renal medulla of both clipped and contralateral kidney. eNOS expression in right and left kidney was not changed despite expected large changes in haemodynamics of the two kidneys. The reduced level of eNOS may be associated with a reduction in MBF and thus be of patho-physiological importance in renovascular hypertension.     

The Effects of Dietary Potassium on Vascular and Glomerular Lesions in Hypertensive Rats

The present study examines the effects of dietary potassium (K) on hypertensive glomerular and vascular lesions in deoxycorticosterone acetate and salt induced (DOCA-salt) and two kidney one clip (2K1C) hypertensive as well as normotensive control rats. Animals received a regular (0.28% K), high (1.1% K) or low (0.07% K) potassium diet for 6 weeks. In control rats, low K diet significantly increased systolic blood pressure (SBP) (p<0.05). In DOCA-salt rats, high K diet did not modify SBP or glomerular and vascular lesions while low K diet significantly increased premature death in these rats. In 2K1C rats, dietary K did not alter the blood pressure, but percentage media area (% media) of intramyocardial arteries, percentage of glomerular lesions, and renal arterial and arteriolar lesion scores were lower in high K diet rats than regular and low K diet rats (p<0.05). This study is the first demonstration that high K diet can protect against vascular and glomerular lesions in a non salt-loaded hypertensive model. The beneficial effects of dietary K on vascular lesions are at least in part independent of changes in blood pressure, and may be renin related.     

高钾饮食对两肾—夹型高血压大鼠血压、肾小球和肾、脾小动脉的影响

用两肾一夹型高血压Wistar大鼠模型观察了高钾饮食对血压、肾小球、肾小管和肾、脾细动脉及小动脉的影响。与普通饮食喂养的高血压大鼠相比,高钾饮食组大鼠血压升高的幅度明显降低(P<0.01),肾小球纤维化和蛋白管型显著减少(P<0.05),高钾组动脉血压的变化与肾细动脉相对内径呈中度负相关(r=-0.575)。提示高钾饮食能抑制两肾一夹型高血压大鼠的血压升高,对肾小球及小脉动有一定的保护作用。     

Comparison of renal and vascular protective effects between telmisartan and amlodipine in hypertensive patients with chronic kidney disease with mild renal insufficiency

The present study was conducted to compare the renal and vascular protective effects of telmisartan and amlodipine in untreated hypertensive chronic kidney disease (CKD) patients with moderate renal insufficiency. Thirty hypertensive CKD patients were randomly assigned to receive telmisartan 40 mg (n = 15) or amlodipine 5 mg (n = 15) once daily for 12 months. Changes in blood pressure, serum creatinine, 24-h creatinine clearance (Ccr), proteinuria, brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT), plasma interleukin-6 (IL-6), plasma matrix metalloproteinase (MMP)-9 and lipid profiles were monitored in all patients. Before treatment, there were no significant differences in these parameters between the telmisartan and amlodipine groups. Over the 12 month observation period, blood pressure decreased equally in both groups. However, serum creatinine, proteinuria, baPWV, IMT, plasma levels of IL-6 and MMP-9 and total cholesterol decreased and 24-h Ccr increased more strikingly in the telmisartan group than the amlodipine group. These data suggest that telmisartan is more effective than amlodipine for protecting renovascular functions, and potentially for ameliorating atherosclerosis, in hypertensive CKD patients with moderate renal insufficiency.