Fluvastatin combined with benazepril may contribute to the favorable prognosis of patients with atrial fibrillation

The aim of this study was to observe the clinical efficacy of fluvastatin combined with benazepril in the treatment of patients with atrial fibrillation (AF). A total of 92 patients with AF were randomly assigned to the case group (n = 46), in which the patients were treated with fluvastatin (80 mg) plus benazepril (10 mg), or to the control group (n = 46), in which the patients were treated with fluvastatin (80 mg). The conversion rate of sinus rhythm was higher in the case group than in the control group (P < 0.05). The case group had more treatment-effective patients than the control group, with fewer treatment-ineffective patients (P < 0.05). The LVEDd, LVESd, LAD, and LVEF indexes in the case group were lower than in the control group after 6 months of treatment (all P < 0.05). Levels of hs-CRP were also lower in patients in the case group than in patients in the control group after 1 month of treatment (P < 0.05). After 12 months, renin and Ang II concentrations were lower in patients in the case group than in the control group (both P < 0.05). Significant differences in IL-6 and TNF-α expression were found between the two groups after 1 month, 6 months, and 12 months of treatment (all P < 0.05). Compared to patients in the control group, the levels of total cholesterol (TC), triglycerides, and LDL-C in the case group were lower after 6 and 12 months of treatment (all P < 0.05), while the HDL level was higher (P < 0.05). Treatment with fluvastatin combined with benazepril further increased the conversion rate of sinus rhythm and significantly improved the quality of life and prognosis of AF patients.     

血浆醛固酮与肾素活性比值测定方法标准化问题的探讨

血浆醛同酮与血浆肾素活性比值(ARR)已广泛应用在高血压患者中筛查原发性醛同酮增多症(原醛).研究表明,不同的临床状况(测定方法)会得出不同的ARR.由于没有统一的ARR标准,使得其临床应用难以适从.因此,应该根据所选用的测定方法和本单位的试验条件,采用相应的,同时具最高敏感性、特异件和准确件的ARR.近年来通过控制测定条件,即所谓测定方法标准化,包括:停用降压药2～4周、取同定体位、上午8:00～12:00之间采血、充分钠摄入以及低血钾者补钾等,发现原醛的ARR范围大致在23.6～26.0 ng·dl-1·ng-1·ml-1·h-1之间,说明ARR筛查方法标准化有助于确定和统一筛查原醛的ARR标准.     

依那普利、厄贝沙坦及血管紧张素-（1—7）对快速心房起搏犬肾素-血管紧张素系统的影响

目的观察快速心房起搏模型犬血管紧张素转换酶2（ACE2）和血管紧张素III型受体（ATlR）mRNA表达的变化,以及应用依那普利、厄贝沙坦及血管紧张素（Ang）-（1-7）对其影响。方法健康成年杂种犬30只,分为5组：假手术组（S组）,心房起搏对照组（C组）,心房起搏＋依那普利组（EN组）,心房起搏＋厄贝沙坦组（IB组）,心房起搏＋血管紧张素-（1-7）组（A组）,每组6只。S组植入起搏器,但不行起搏刺激及药物干预。C组植入起搏器并起搏,但无药物干预。EN组及IB组分别于起搏开始前3d开始给予口服依那普利2mg·kg^-1·d^-1或厄贝沙坦60mg·kg^-1·d^-1。A组给予Ang-（1-7）6μg·kg^-1·h^-1持续静脉泵人。各组犬经500次／min快速心房起搏2周后,采集右心房肌标本,逆转录聚合酶链式反应（RT—PCR）检测心房肌组织中ACE2和ATlRmRNA表达。结果心房起搏组较假手术组ACE2表达降低,ATlR表达明显升高,应用依那普利、厄贝沙坦和Ang－（1-7）可使ACE2表达增加和ATIR水平下调。结论快速心房起搏2周可诱发心脏局部肾素－血管紧张素（RAS）系统的活化,依那普利、厄贝沙坦和Ang－（1-7）可抑制起搏后的RAS系统激活,降低心房颤动的易感性。Ang－（1-7）的心脏保护作用可能通过下调ATIR和上调ACE2来介导。     

血管紧张素Ⅱ调节肾脏球旁器颗粒细胞合成肾素的机制研究

目的 观察血管紧张素Ⅱ（AngⅡ）对肾脏球旁器颗粒细胞肾素分泌的调节作用。 方法 密度梯度离心原代分离小鼠肾小球球旁器颗粒细胞（JGC）。实时定量PCR法检测JGC内血管紧张素转换酶（ACE）、AngⅡ受体（AT）1型和2型（AT1和AT2） mRNA表达。不同浓度的AngⅡ与球旁器细胞共孵育后,放射免疫法测定上清中肾素活性;实时定量PCR法测定细胞内肾素mRNA表达;化学发光法测定细胞内、外环磷酸腺苷（cAMP)水平的剂量和时间效应。改变细胞内钙离子浓度后,观察JGC内和上清中cAMP浓度改变。实时定量PCR法检测AngⅡ对JGC内腺苷酸环化酶（AC）5和AC6 mRNA表达的影响。 结果 成功分离的JGC存在ACE、AT基因表达。AngⅡ可抑制JGC肾素分泌[（370.6±36.9）比（299.6±25.7） ng AngI&#8226;ml-1&#8226;h-1,P = 0.014],并能抑制基础状态和前列腺素E2、去甲肾上腺素诱导的肾素mRNA表达。AngⅡ剂量依赖地降低JGC内和上清中cAMP水平。内质网上的Ca-ATP泵抑制剂毒胡萝卜内酯和环盐酸吗甲吡嗪酸均能剂量依赖地降低cAMP水平。细胞内钙离子螯合剂BAPTA-AM可降低细胞内钙离子浓度,进而使细胞内cAMP水平显著升高[（11.09±0.48）比（3.55±0.47） nmol/L,P < 0.01]。AngⅡ能通过减少42.12%的AC5 mRNA 表达,进而抑制肾素分泌。 结论 AngⅡ直接抑制肾素分泌可能是通过影响AC5,进而抑制cAMP表达来实现的。JGC内调节肾素分泌过程中,钙离子途径和GSα-cAMP两大信号传导途径中存在交联对话。     

不同血液净化方式对心血管稳定性影响的临床研究

目的 比较不同血液净化方法对慢性肾功能衰竭(CRF)患者心血管稳定性的影响及其内在可能机制.方法 将90例CRF患者随机分为3组.A组(HD组)行每周3次标准血液透析(HD)治疗;B组(HDF组)行每周2次常规标准血液透析(HD)治疗和每周1次血液透析滤过(HDF)治疗;C组(HP组)行每周2次常规标准血液透析(HD)...     

前列腺素E2在肾脏球旁器调节肾素分泌中的作用

目的 观察前列腺素E2（PGE2）对肾脏球旁器颗粒细胞（JGG）肾素分泌的调节作用。 方法 将小鼠肾脏致密斑细胞株（MMDD1）种植在特殊滤器上,滤器上下（细胞顶侧和基底侧）分别用不同培养基培养细胞,改变细胞顶侧培养基中钠离子、氯离子和血管紧张素Ⅱ（AngⅡ）浓度,分别测定不同时间点滤器上、下PGE2浓度。腹腔注射卡托普利（30 mg/kg）前后,放射免疫法测定野生型和环氧化酶基因敲除（COX-2-/-）小鼠血浆肾素活性(PRA)变化;原代分离COX-2-/-小鼠JGG,测定细胞上清肾素活性及其对PGE2刺激的反应。实时定量PCR测定低肾素（JGG细胞特异性Gsα基因缺失）小鼠肾脏皮质COX-2 mRNA表达。免疫组化法检测肾皮质COX-2蛋白表达。代谢笼中留取24 h尿,ELISA方法测定PGE2水平。 结果 (1)低氯刺激能使致密斑细胞分泌PGE2,不论基底侧还是细胞顶端PGE2浓度均显著增加（均P < 0.05）;但AngⅡ对致密斑分泌PGE2没有显著影响;(2)COX-2-/-小鼠基础PRA[（378.3±96.4）比（1115.0±210.0） ng AngI&#8226;ml-1&#8226;h-1,P ＝ 0.0051,n＝10]和JGG细胞肾素分泌[（153.7±14.7）比（672.4±129.0） ng AngI&#8226;ml-1&#8226;h-1,P ＝ 0.0162,n＝3]显著低于相同遗传背景的野生型小鼠;卡托普利能刺激COX-2-/-小鼠PRA增加32.8倍;PGE2能部分恢复COX-2-/-小鼠原代JGG细胞分泌肾素功能;(3)PGE2受体EP4耦联的Gsα基因敲除的低肾素小鼠,肾脏皮质COX-2 mRNA表达增加（8.07±1.08)倍（n=6,P = 0.0022),免疫组化显示致密斑和远端小管COX-2蛋白表达增加,24 h尿PGE2分泌增加[（1235±152） pg/24 h 比（385±140） pg/24 h,P = 0.0065]。 结论 致密斑PGE2直接受低氯调节,COX-2-/-小鼠基础肾素减少;下游的AngⅡ能直接作用于JGG细胞而不是致密斑负反馈调节肾素分泌。阻断JGG细胞自身的肾素产生（Gsα基因敲除）后,能负反馈上调致密斑的COX-2表达,故COX-2-PGE2-肾素在球旁器存在近距离精确调控机制。     

依普利酮对醛固酮输注大鼠肾脏肾素受体表达的影响

目的：探讨依普利酮（Epl）对醛固酮（ALD）输注大鼠肾脏肾素受体表达的影响。方法：18只SD大鼠随机分为3组：对照组、ALD输注组、Epl治疗组,均皮下埋置渗透性微泵,其中ALD输注组、Epl治疗组持续输注ALD（1．5ug·h^-1）,Epl治疗组同时给予依普利酮（100mg·kg^-1·d^-1）灌胃,对照组、ALD输注组以等量生理盐水灌胃。隔周测量尾动脉压,收集24h尿液测定尿白蛋白排泄率（UAER）,于第28天处死动物。PAS染色观察肾组织病理改变,RT—PCR法检测肾素受体表达,免疫组化染色检测肾素受体表达。结果：ALD输注组大鼠血压、UAER较对照组显著升高（P〈0．05）,Epl治疗组大鼠血压、UAER显著低于ALD输注组（P〈0．05）;ALD输注组大鼠肾小球系膜细胞增殖伴系膜外基质增多,Epl治疗组肾小球病理变化较ALD输注组显著减轻;肾素受体主要分布于肾小球系膜细胞,Epl治疗组肾素受体mRNA显著低于ALD输注组（P〈0．05）。结论 依普利酮能显著减少ALD输注大鼠肾脏肾素受体表达,减轻ALD诱导的大鼠肾脏损伤。     

巨细胞病毒感染对细胞肾素基因表达的影响及其生物学意义

目的 探讨巨细胞病毒(cytomegalovirus,CMV)感染肾球旁细胞肾素基因表达的变化及其意义.方法 用病毒感染复数(MOI)为10、0.1和0的鼠CMV分别与鼠肾球旁细胞模型As4.1细胞共育5 d作为实验组;用紫外线灭活病毒的假感染(mock感染)对照组.RT-PCR检测感染细胞中CMV即刻早期基因1(IE1)的表达;免疫荧光观察肾素阳性细胞和肾素阳性颗粒在细胞的分布;双色免疫荧光染色观察肾素阳性颗粒是否出现在CMV阳性细胞;RT-PCR和Western blot检测肾素基因在感染细胞内的表达.结果 CMV感染As4.1细胞后出现典型的病毒空斑;病毒感染细胞CMV IE1 RT-PCR产物阳性;肾素阳性细胞集中在病毒空斑周围CMV新感染细胞区,肾素阳性荧光颗粒主要以块状和环状存在于病毒感染细胞质中;双色免疫荧光染色显示肾素阳性颗粒和CMV阳性颗粒出现在同一细胞;CMV感染细胞肾素基因的表达随病毒感染量增加而增加.结论 CMV感染并导致其宿主细胞肾素基因表达,可能涉及CMV加速心血管疾病发生发展的新机制.     

The biochemical pharmacology of renin inhibitors: Implications for translational medicine in hypertension, diabetic nephropathy and heart failure: Expectations and reality

The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, Diabetes mellitus (DM), chronic kidney disease (CKD) and chronic heart failure (CHF). Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEi or ARBs remain high. Small molecules that directly inhibit renin (DRI) and are orally active have also been developed and one such drug, aliskiren, was introduced into clinical use for treatment of hypertension in 2007. Further clinical trials aimed to expand the therapeutic use of aliskiren are in progress for CKD-DM and CHF. In this review we analyze and review the translational medicine prospects of aliskiren in respect to the biochemical pharmacology of the RAAS, the marketed RAAS modulators and the new emerging science regarding the role of prorenin, renin and renin receptors in cardiovascular biology and disease. The information already gained with aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEis and ARBs, their potential added value in combination with other RAAS modulators and other unproven benefits in relation to prorenin and renin receptor biology. This review will also indicate basic and clinical research needs that are critical to determine whether DRIs can provide meaningful added medical benefits over contemporary medicines that regulate the RAAS, and the need to identify patients that are more likely to benefit from DRIs and any possible long term adverse effects.