坎地沙坦抑制盐负荷高血压大鼠肾脏氧化应激

目的探讨血管紧张素Ⅱ（AngⅡ）受体拮抗剂坎地沙坦对盐负荷易卒中自发性高血压大鼠（SHR—SP）肾脏氧化应激和氧化型低密度脂蛋白受体1（LOX-1）表达的影响。方法12周龄Wistar-Kyoto（wKY）大鼠和SHRSP予8％高盐饮食。高盐WKY大鼠（n=6）作为对照组，高盐SHRSP随机分为3组：1）坎地沙坦组（Can，n=6），Can1．0mg／（kg·d）灌胃；2）三氯噻嗪组（TCM，n=6），TCM1．6mg／（kg·d）；3）SHRSP组（n=6），给予等量溶媒。用尾部袖套测量法每周检测1次血压。大鼠给药2周后摘取肾脏，留取24h尿量。采用实时定量PCR检测肾脏NAD（P）H氧化酶亚单位p22phox、p47phox和gp91phox mRNA表达，RT—PCR方法检测LOX-1、转化生长因子β1（TGF—β1）和Ⅳ型胶原mRNA的表达。免疫组化检测肾组织gp91phox和LOX-1蛋白表达，ELISA方法检测尿白蛋白排泄，放免法检测肾脏AngⅡ水平，天狼猩红染色观察肾组织胶原表达。结果实验2周后，SHRSP组收缩压显著高于对照组（P〈0．01），Can和TCM均降低高盐SHRSP组的收缩压（P〈0．01），二者间的降压幅度无差别（P〉0．05）。与对照组比较，肾皮质NAD（P）H氧化酶亚单位、LOX-1、TGF-β1和Ⅳ型胶原mRNA的表达、肾组织AngⅡ水平和尿白蛋白排泄，SHRSP组显著增高；Can降低高盐SHRSP肾组织AngⅡ水平（P〈0．01），下调肾皮质NAD（P）H氧化酶亚单位、LOX-1、TGF-β1和Ⅳ型胶原mRNA的表达（P〈0．01），减少尿白蛋白的排泄（P〈0．01），减轻肾组织胶原的沉积。等效降压剂量的TCM对高盐SHRSP肾组织NAD（P）H氧化酶亚单位、LOX-1的表达和尿白蛋白水平无明显影响。结论Can对盐负荷SHRSP的肾脏保护作用，与抑制氧化应激和LOX-1表达有关，可能不一定依赖其降压作用。     

坎地沙坦酯治疗高血压的临床研究

目的观察坎地沙坦酯治疗高血压的疗效与安全性。方法将30例患者分为3组进行对比研究。结果 1组换用坎地沙坦西酯片后全部不良反应消失;2组6周时58.3%的患者血压降至正常;3组6周时血压全部降至正常。结论坎地沙坦西酯片是一种有效、耐受性好的降压药物。     

坎地沙坦对伴有高血压的急性卒中患者无益

在卒中急性期出现高血压的患者中应用坎地沙坦不能提供任何益处,相反可能有害。卒中急性期高血压管理的最佳方法尚不清楚,目前的做法是接受这种情况下的高血压。     

非洛地平联合坎地沙坦治疗高血压40例疗效观察

目的观察非洛地平联合坎地沙坦的降压疗效。方法将80例高血压病病人随机分为非洛地平组(B组,20例)、坎地沙坦组(C组20例)及联合用药组(A组,40例),疗程均为8周,观察3组的降压疗效。结果A组总效率为97.5%,B组为70.0%,C组为60.0%。结论非洛地平联合坎地沙坦治疗高血压优于其中单一药物治疗。     

坎地沙坦酯片治疗高血压的疗效观察

目的观察坎地沙坦酯片治疗高血压的临床疗效及安全性。方法将我院2010年2月—2011年1月收治的120例老年高血压患者随机平均分为两组,治疗组60例采用坎地沙坦酯片8mg/次,1次/d口服治疗;对照组60例采用卡托普利37.5～75.0mg/d。两组治疗3个月为1个疗程,观察并对比两组临床疗效及安全性。结果治疗组治疗后收缩压、舒张压与对照组比较,差异有统计学意义(P<0.05)。治疗组总有效率为90%;对照组总有效率为76.7%。两组临床疗效比较,差异有统计学意义(P<0.05)。结论坎地沙坦治疗高血压临床疗效安全、平稳、疗效好,能够有效控制高血压。     

苯那普利与坎地沙坦减轻自发性高血压大鼠主动脉内皮氧化应激

目的 观察苯那普利、坎地沙坦治疗对自发性高血压大鼠(SHR)主动脉内皮氧化应激以及内皮型一氧化氮合酶(eNOS)、NAD(P)H氧化酶重要亚单位P22phox表达的作用. 方法 12周龄SHR(n=9)连续灌胃给予苯那普利[10 mg/(kg·d),n=9]或(和)坎地沙坦[4 nag/(kg·d),n=9],每2周测定尾动脉压.12周后检测主动脉病理结构、血清超氧化物歧化酶(SOD)活力、一氧化氮(NO)和羟自由基的含量、血浆血管紧张素Ⅱ(AngⅡ)和环鸟苷酸(cGMP)水平、主动脉内膜eNOS和P22phox的表达. 结果 SHR主动脉血管壁明显增厚,尾动脉压、血清羟自由基、血浆AngⅡ水平及主动脉P22phox的表达均显著增高,而血清SOD活力、NO含量、cGMP水平及血管组织eNOS的表达均降低.应用苯那普利(Ben)、坎地沙坦(Can)单独治疗均可改善自发性高血压大鼠主动脉结构,增加血清SOD活力[Ben:(68.7±2.1),Can:(65.6±4.2)比SHR:(48.8±3.2)U/mL,P＜0.01]、NO含量[Ben:(60.2±3.5),Can:(58.3±4.4)比SHR:(42.7±2.9)μmol/L,P＜0.01]、血浆cGMP含量[Ben:(8.7±1.3),Can:(8.0±1.2)比SHR:(5.0±1.1)pmol/mL,P＜0.01]及主动脉eNOS表达[Ben:(1.1±0.3),Can:(1.1±0.2)比SHR:(1.0±0.2),P＜0.01],减少血清羟自由基量[Ben:(422±27),Can:(428±39)比SHR:(616±50)U/mL,P＜0.01和P＜0.05]及主动脉P22phox的表达[Ben:(1.0±0.2),Can:(1.1±0.2)比SHR:(1.7±0.4),P＜0.01];两药联用[苯那普利5 mg/(kg·d) 坎地沙坦2 mg/(kg·d)]能增加NO含量及eNOS表达、降低P22phox表达,虽然与两药单独使用没有统计学意义,但是在增加SOD活力[(71.6±4.2)U/mL]、cGMP含量[(10.2±1.2)pmol/mL]及减少羟自由基含量[(399±50)U/mL]效果较好(与Can组相比,P＜0.05). 结论 苯那普利和(或)坎地沙坦单用均能够改善SHR主动脉结构及氧化应激状态,两者联合应用具有部分协同作用.     

坎地沙坦与福辛普利对高血压疗效的观察

目的前瞻性评估坎地沙坦治疗原发性高血压的降压疗效和安全性。方法130例轻中度原发性高血压患者随机服用坎地沙坦4~8mg或福辛普利10~20mg共20周,服药前后行动态血压监测(ABPM),观察24h收缩压(SBP)和舒张压(DBP)、谷峰比值、下一次给药前6h血压变化、降压有效率和不良反应。结果坎地沙坦和福辛普利均能有效降低血压,20周治疗有效率分别为74%和73%(P>0.05),坎地沙坦谷峰比值较福辛普利高(SBP:79%VS63%,P<0.05;DBP:79%vs62%P<0.05;),且较福辛普利具有更强的减低清晨2:00~8:00血压的作用(P<0.05)。坎地沙坦不良反应发生率较少。结论坎地沙坦治疗轻中度原发性高血压安全有效,耐受性好,可持续24h理想的控制血压。     

坎地沙坦对高血压患者窦性心率震荡现象的影响

目的观察高血压患者的窦性心率震荡（HRT）现象及坎地沙坦治疗对其的影响。方法应用24 h动态心电图比较2级以上原发性高血压患者（治疗组）治疗（8-16 mg坎地沙坦,每日1次）前后及健康对照者（对照组）的HRT指标[震荡初始（TO）、震荡斜率（TS）]的变化。结果与对照组相比,治疗组TO升高,TS降低（P〈0.01）。治疗组治疗后血压明显下降,TO降低,TS升高（P〈0.01或〈0.05）。结论高血压患者HRT现象明显减弱,提示存在自主神经功能受损;坎地沙坦可有效降压,并可改善高血压患者的自主神经功能。     

坎地沙坦酯与依那普利治疗原发性轻中度高血压疗效比较

高血压是最常见的心血管疾病之一，严重威胁着人类的健康，是引起脑卒中、心力衰竭和冠心病等的危险因素。高血压治疗的目的不仅仅是降低血压，更重要的是保护脑、心、肾等靶器官，降低相关心血管疾病的发生率、致死率和致残率，改善患者生活质量，延长患者寿命。笔者回顾性分析近1年来经坎地沙坦酯和依那普利治疗原发性轻、中度高血压患者的临床资料，评价国产坎地沙坦酯治疗轻、中度高血压的临床疗效及安全性。     

广谱基质金属蛋白酶抑制剂对高血压肾纤维化的影响

目的研究多西环素(DOX)对卒中易感型自发性高血压大鼠(SHR-SP)肾脏基质金属蛋白酶(MMPs)及金属蛋白酶组织型抑制剂(TIMPs)活性的影响,探讨DOX对高血压肾纤维化病理转归的作用机制。方法选用7周龄雄性SHR-SP随机分为药物干预组和对照组,定期观察大鼠体重、测量无创鼠尾压、尿量、尿肌酐、尿蛋白变化。观察终止时进行血流动力学分析;测定血清肌酐、尿素氮浓度;采用组织病理、明胶酶谱和逆明胶酶谱等方法观察各组大鼠肾脏组织学改变和MMP-2、MMP-9、TIMP-1、TIMP-2等活性变化。结果收缩压、脉压、血清肌酐浓度在DOX组与对照组之间无统计学差异,但DOX组有升高趋势;从19周龄起,DOX组大鼠尿蛋白浓度与尿肌酐浓度比值即高于对照组[(8·3±6·4vs3·3±2·0)mg/μmol,P<0·05];病理染色显示肾小管损伤平均指数和胶原容积分数均高于对照组(损伤平均指数:3·14±0·47vs2·69±0·38,P<0·05;胶原容积分数:10·5%±2·7%vs6·6%±1·9%,P<0·01);与血压正常大鼠相比,高血压大鼠肾脏MMP-2、MMP-9、TIMP-1和TIMP-2的活性升高;药物干预后MMP-2、MMP-9活性降低(MMP-2:2·62±0·75vs3·39±0·92;MMP-9:2·89±1·13vs4·01±0·91,P<0·05),而TIMP-1、TIMP-2活性则显著升高(TIMP-1:2·89±1·76vs1·54±0·86,P<0·05;TIMP-2:1·69±0·47vs1·06±0·47,P<0·01)。结论广谱基质金属蛋白酶抑制剂DOX可以抑制SHR-SP肾脏中MMP-2、MMP-9活性,加重高血压造成的肾脏损害。在肾脏损害发生后,抑制MMPs活性可能会加重高血压肾脏纤维化的进展。     

广谱基质金属蛋白酶抑制剂对高血压肾纤维化的影响

目的 研究多西环素(DOX)对卒中易感型自发性高血压大鼠(SHR-SP)肾脏基质金属蛋白酶(MMPs)及金属蛋白酶组织型抑制剂(TIMPs)活性的影响,探讨DOX对高血压肾纤维化病理转归的作用机制.方法 选用7周龄雄性SHR-SP随机分为药物干预组和对照组,定期观察大鼠体重、测量无创鼠尾压、尿量、尿肌酐、尿蛋白变化.观察终止时进行血流动力学分析;测定血清肌酐、尿素氮浓度;采用组织病理、明胶酶谱和逆明胶酶谱等方法观察各组大鼠肾脏组织学改变和MMP-2、MMP-9、TIMP-1、TIMP-2等活性变化.结果 收缩压、脉压、血清肌酐浓度在DOX组与对照组之间无统计学差异,但DOX组有升高趋势;从19周龄起,DOX组大鼠尿蛋白浓度与尿肌酐浓度比值即高于对照组[(8.3±6.4 vs 3.3±2.0)mg/μmol,P＜0.05];病理染色显示肾小管损伤平均指数和胶原容积分数均高于对照组(损伤平均指数:3.14±0.47 vs 2.69±0.38,P＜0.05;胶原容积分数:10.5%±2.7% vs 6.6%±1.9%,P＜0.01);与血压正常大鼠相比,高血压大鼠肾脏MMP-2、MMP-9、TIMP-1和TIMP-2的活性升高;药物干预后MMP-2、MMP-9活性降低(MMP-2:2.62±0.75 vs 3.39±0.92;MMP-9:2.89±1.13 vs 4.01±0.91,P＜0.05),而TIMP-1、TIMP-2活性则显著升高(TIMP-1:2.89±1.76 vs 1.54±0.86,P＜0.05;TIMP-2:1.69±0.47 vs 1.06±0.47,P＜0.01).结论 广谱基质金属蛋白酶抑制剂DOX可以抑制SHR-SP肾脏中MMP-2、MMP-9活性,加重高血压造成的肾脏损害.在肾脏损害发生后,抑制MMPs活性可能会加重高血压肾脏纤维化的进展.     

葛根素（普乐林）对SHRsp脑卒中预防和治疗作用的研究

目的：研究普乐林注射液对卒中型自发性高血压大鼠（ＳＨＲｓｐ）脑卒中的预防和治疗作用。材料和方法：将８０只周龄（雌雄各半）ＳＨＲｓｐ随机分为普乐林２００ｍｇ／ｋｇ,１００ｍｇ／ｋｇ及对照组,饮１．０％～１．５％,ＮａＣｌ盐水。实验一,在高盐负荷开始即灌胃治疗,８周后断头处死,取颈动脉及脑组织做电镜检查。取脑组织光镜下检查脑卒中发生率。实验二;脑卒中发生后开始灌胃治疗,连续１０天,记录大鼠脑卒中临床表     

蛋白质摄入对卒中型自发性高血压大鼠脑卒中及繁育能力的影响

本实验结果提示在饲料中适当增加蛋白质含量．既可保持卒中型自发性高血压大鼠（SHRsp）脑卒中的特性（脑卒中病理检出率为86．6％），又保持了大鼠正常的繁育能力及身体健康，显著延长了雌鼠的寿命，增加了雄鼠及仔鼠的体重。     

Genetically Altered Brain Amino Acid Metabolism in Spontaneously Hypertensive Rats: A Study by Using Young Spontaneously Hypertensive Rats and Renal Hypertensive Rats

Previously we demonstrated altered amino acid levels in brain-stem regions of adult spontaneously hypertensive rats (SHR). For comparison, in this study, we determined amino acid concentrations in discrete brainstem regions in young prehypertensive SHR and renal hypertensive rats. In prehypertensive SHR, the content of glutamate was increased in the rostral ventrolateral medulla and the causal ventrolateral medulla, and the content of β–alanine was decreased in the nucleus tractus solitarii. In renal hypertensive rats, there was no change in glutamate and β–alanine contents in all the regions. The profiles of contents of glutamate and β–alanine in the brain-stem regions in young SHR but not in renal hypertensive rats are the same as those found previously in adult SHR. Thus, the results of the present study suggest that the altered amino acid metabolism in the brainstem of SHR may be genetically inherent.     

拉西地平对高血压大鼠的降压作用

目的：观察新的钙拮抗剂拉西地平的降压作用。方法：急性降压实验：将５个月龄雄性卒中型自发性高血压大鼠（ＳＨＲｓｐ）随机分为Ａ、Ｂ、Ｃ（分别经管饲给药１次，拉西地平剂量１ｍｇ／ｋｇ，０．５ｍｇ／ｋｇ，０．２５ｍｇ／ｋｇ）、Ｄ（尼群地平１０ｍｇ／ｋｇ）、Ｅ（溶媒对照）组，每组１１只，于用药后１、３、５、９、１２、２４小时各测１次收缩压及心率（尾套法）。慢性降压实验：将３个月龄ＳＨＲｓｐ分为Ａ、Ｂ、Ｄ、Ｅ组（剂量同急性降压实验），每组１０只，治疗１４天，于治疗后第２、４、６、８、１０、１２、１４天各测１次收缩压及心率。结果：拉西地平１ｍｇ／ｋｇ和０．５ｍｇ／ｋｇ均可显著降低ＳＨＲｓｐ血压，降压作用分别持续１２～２４小时和９～１２小时，降压作用均强于尼群地平１０ｍｇ／ｋｇ，仅轻度增加了心率。结论：拉西地平对ＳＨＲｓｐ降压作用明确，持续时间长。     

Effects of Long-Term Treatment with Candesartan on Hemodynamics and Organ Damage in Spontaneously Hypertensive Rats

Summary This study was designed to investigate the effects of candesartan on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in spontaneously hypertensive rats (SHR). Methods: Studies were performed in two groups of SHR (n = 13 for control rats; and n = 20 for candesartan-treated rats) and one group of WKY rats (n = 13). Candesartan (3mg /kg/d) was given in rat chow for 4 months. BP was then continuously recorded for 24 hours in conscious state. After the determination of BRS, rats were killed for organ-damage evaluation. Results: Long-term treatment with candesartan significantly reduced BP and BPV expressed by both standard deviation and variation coefficient of BP, enhanced BRS and produced obvious organ protection. Compared with BP level, BPV and BRS values showed a closer or similar relationship with organ-damage parameters in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was most closely associated with the increase in BRS, whereas the decrease in aortic hypertrophy was most closely associated with the decrease in 24-hour systolic BPV, and the amelioration in renal lesions, with the increase in BRS and the decrease in 24-hour systolic BPV. Conclusion: long-term treatment with candesartan results in organ protection in SHR. Besides BP reduction, the decrease in BPV and the restoration of BRS are significantly related to this organ protection.     

Renal Protective Effects of Efonidipine in Partially Nephrectomized Spontaneously Hypertensive Rats

We investigated the effects of a calcium antagonist, efonidipine, which was reported to dilate not only afferent arterioles but also efferent arterioles, on progression of renal failure in salt-loaded partially nephrectomized spontaneously hypertensive rats (SHR). Forty-four SHR's with 5 of 6 nephrectomy were divided into four groups: group 1 as control (n=20); group 2, efonidipine-treated (n=8); group 3, enalapril-treated (n=8); and group 4, nifedipine-treated (n=8). The rats were given these drugs and a high-salt diet (5% NaCl) for 8 weeks. During the experiment, systolic blood pressure (SBP) and daily urinary protein excretion were measured eveiy 2 weeks. At the end of the study. seniin creatinine was deteimined, and renal tissues were obtained for light microscopic examination. SBI was markedly reduced by 8-week antihypertensive treatment. (control, 267±7 mmHg: efonidipine, 181 ± 7 mmHg; enalapril, 200±12 mmHg; nifedipine, 184±6 mmHg). Glomerular sclerosis developed markedly in the control group, but was partially prevented in all treated groups. Similarly, urinary protein excretion (UPE) was suppressed by efonidipine (180±16 mg/day) and enalapril (180±16 mg/day vs. 301±28 mg/day for control). In contrast, nifedipine failed to prevent the increase in urinaiy protein excretion (258±22 mg/day). In conclusion, efonidipine attenuates SBP increase and ameliorates glomerular injuty as well as nifedipine and enalapril. Furthermore, beneficial effects of efonidipine, but not nifedipine, on proteinuria suggest that different mechanisms mediate the improvement of proteinuria; one possible mechanism could be efferent arteriolar dilation, not reported in nifedipine.