Telmisartan prevents cardiovascular events in a broad group of at-risk patients

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET^?) was a 25,620 patient study program comparing telmisartan with ramipril or the combination thereof in patients at increased cardiovascular risk. Ramipril had previously been proven to prevent cardiovascular events in a similar population within the HOPE-trial. However, ramipril and other ACE inhibitors (ACE-Is) may have limited tolerability that might restrict their use in patients requiring secondary prevention, whereas angiotensin receptor blockers (ARBs) are suggested to be better tolerated. However, no ARB had been compared with the standard treatment, ramipril, in these cardiovascular patients at increased risk. ONTARGET showed that telmisartan was as effective as ramipril in preventing cardiovascular events, but was better tolerated. The combination of ramipril and telmisartan was not superior to either monotherapy. Taken together, ONTARGET demonstrated that telmisartan is as effective as ramipril in a broad cardiovascular increased-risk population in the middle of the cardiovascular continuum. In these patients who are intolerant to ACE-Is or who do not achieve blood pressure control, the ARB with the best evidence for secondary prevention is telmisartan according to the results of the ONTARGET trial.     

RP-HPLC Estimation of Ramipril and Telmisartan in Tablets

A rapid high performance liquid chromatographic method has been developed and validated for the estimation of ramipril and telmisartan simultaneously in combined dosage form. A Genesis C18 column having dimensions of 4.6×250 mm and particle size of 5 μm in isocratic mode, with mobile phase containing a mixture of 0.01 M potassium dihydrogen phosphate buffer (adjusted to pH 3.4 using orthophosphoric acid): methanol:acetonitrile (15:15:70 v/v/v) was used. The mobile phase was pumped at a flow rate of 1.0 ml/min and the eluents were monitored at 210 nm. The selected chromatographic conditions were found to effectively separate ramipril (R_t: 3.68 min) and telmisartan (R_t: 4.98 min) having a resolution of 3.84. The method was validated in terms of linearity, accuracy, precision, specificity, limit of detection and limit of quantitation. Linearity for ramipril and telmisartan were found in the range of 3.5-6.5 μg/ml and 28.0-52.0 μg/ml, respectively. The percentage recoveries for ramipril and telmisartan ranged from 99.09-101.64% and 99.45-100.99%, respectively. The limit of detection and the limit of quantitation for ramipril was found to be 0.5 μg/ml and 1.5 μg/ml respectively and for telmisartan was found to be 1.5 μg/ml and 3.0 μg/ml, respectively. The method was found to be robust and can be successfully used to determine the drug content of marketed formulations.     

颈动脉粥样硬化、血管内皮舒张功能与冠心病的相关性分析

目的研究分析冠心病患者颈动脉粥样硬化与血管舒张功能的相关性。方法选取2012年12月～2013年12月期间收治的45例冠心病患者为试验组,并选取同期体检的45例无冠心病患者为对照组。应用高频超声检查全部患者的血管内皮舒张功能（EDD）、颈动脉斑块数、颈动脉内一中膜厚度（IMT）以及颈动脉斑块积分。结果试验组患者的颈动脉斑块数、IMT、颈动脉斑块积分均大于对照组,差异有统计学意义（P〈0．05）;试验组患者EDD明显小于对照组,差异有统计学意义（P〈0．05）。结论血管内皮舒张功能、颈动脉粥样硬化与冠心病的发病具有紧密联系,两者是临床预防冠心病的关键指标。     

The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction

Objective: To investigate the impact of daily sildenafil on levels of soluble molecular markers of endothelial function in men with erectile dysfunction. Methods: Patients aged > 18 years with erectile dysfunction of vascular etiology for > 6 months, either alone or in combination with disease states strongly associated with endothelial dysfunction such as diabetes/metabolic syndrome, hypertension and coronary artery disease, received sildenafil 25 mg orally for 4 weeks. Markers of endothelial function were measured in plasma at baseline and at end of treatment using standard methods and commercially available kits. Results: Altogether, 112 men with mean (SD) age of 60.6 (7.3) years completed the protocol. Sildenafil 25 mg daily for 4 weeks significantly reduced endothelin-1 levels compared with baseline (2.83 ± 1.63 vs 3.24 ± 1.90 pg/ml, p < 0.001). Significant changes were also observed for nitric oxide (35.12 ± 21.14 vs 31.91 ± 16.28 pmol/lt, p = 0.01) and cyclic guanosine monophosphate (3.79 ± 2.37 vs 2.70 ± 1.34 pmol/ml, p < 0.001) levels, but not for any of the other biomarkers measured. Erectile function was significantly improved. Conclusions: Daily sildenafil ameliorates endothelial function as assessed by levels of biomarkers of endothelial function in patients with erectile dysfunction. This is in agreement with other studies showing similar benefits with phosphodiesterase-5 inhibitor treatment. The clinical implications of this finding warrant further investigation.     

瑞舒伐他汀联用雷米普利对高血压患者血清hs-CRP及MMP9水平的影响

目的:本文分析瑞舒伐他汀联用雷米普利对高血压患者血清hs-CRP及MMP9水平的影响,为相关临床诊断及治疗提供参考。 方法:回顾性分析我院2011年11月至2013年11月期间诊治的高血压患者临床资料。所有260例患者随机分为2组:对照组(n=130)给予雷米普利(5 mg·d^-1)治疗,观察组(n=130)联合应用瑞舒伐他汀(20 mg·d^-1)和雷米普利(5 mg·d^-1)进行治疗。分析2组患者治疗前后的hs-CRP、MMP9水平变化和心肌收缩、舒张压变化及TG、TC、HDL-C和LDL-C水平变化。2组疗程均为6个月,同时观察患者的心血管事件发生率,健康体检者为对照。结果:高血压患者血清hs-CRP、MMP9水平和LVSP/LVEDP均明显增高,且血脂指标发生异常。观察组患者和对照组患者在治疗后上述异常均得到改善,且2组之间存在显著的统计学差异性(P<0.05)。结论:瑞舒伐他汀联用雷米普利能够有效缓解高血压患者血脂异常及血清hs-CRP及MMP9升高,恢复心肌收缩舒张功能,具有很好的临床推广意义。     

The acute haemodynamic and renal effects of oral felodipine and ramipril in healthy subjects

Summary The aim of the present investigation was to compare the acute haemodynamic and renal effects of the calcium antagonist felodipine with the ACE inhibitor ramipril and with placebo.Single oral doses of felodipine 5 and 20 mg, ramipril 2.5 and 10 mg, and placebo were given to ten healthy subjects in a double-blind cross-over study. Blood pressure, heart rate, forearm blood flow (FBF), forearm vascular resistance (FVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), diuresis, and sodium excretion were recorded for 4.75 h after administration.Felodipine 20 mg caused a significant fall in diastolic blood pressure, maximal 12 % compared with placebo, while there were no significant effects of felodipine 5 mg or the two doses of ramipril. Heart rate increased significantly after both doses of felodipine, maximal 28% after the 20 mg dose. There was also a small but significant increase in heart rate of 12% after ramipril 2.5 mg. FVR fell significantly after both doses of felodipine, maximal 38 % after the 20 mg dose. There were no significant changes in FVR after any of the ramipril doses. Both doses of felodipine and both doses of ramipril caused significant reductions in RVR. Maximal reduction, 33 %, was found after felodipine 20 mg. There were no significant changes in GFR or FF with either drug. Felodipine caused a significant increase in natriuresis, maximal 129% while ramipril did not.     

雷米普利对大鼠高血压并发左心室心肌肥厚伴心肌舒张功能不全和血管纤维化的作用

目的探讨雷米普利对舒张性心力衰竭的治疗作用。方法45只雄性Spargue-Dawley大鼠随机分为假手术组、心肌肥厚模型组和雷米普利治疗组。采用腹主动脉缩窄手术制备心肌肥厚模型,造模12周后ig给予雷米普利1mg·kg-1,每天1次,连续12周。颈动脉插管法测定大鼠左心室舒张末压(LVEDP)、左心室收缩压(LVSP)和左心室压变化速率最大值(±dp/dtmax);测定心脏重量指数和左心室重量指数(LVMI);Van Gieson染色法测定心肌间质和心肌血管纤维化程度;实时PCR法测定胶原Ⅰ型和胶原Ⅲ型mRNA表达。结果与假手术组相比,模型组大鼠LVEDP和LVSP分别升高了103.9%和37.7%;LVMI、心肌间质和血管纤维化分别增加了35.5%,306.3%和104.1%;胶原Ⅰ型和胶原Ⅲ型mRNA表达分别上调2.1倍和4.4倍。与模型组大鼠比较,雷米普利组大鼠LVEDP,LVSP和LVMI分别降低了62.5%,27.4%和18.6%;大鼠心肌间质和心肌血管的纤维化分别降低了44.9%和55.6%;心肌组织胶原Ⅰ型和胶原Ⅲ型mRNA表达分别降低了44.8%和67.0%。结论雷米普利能改善高血压并发左心室心肌肥厚伴心肌舒张功能不全大鼠的心肌舒张功能,可能与其延缓心肌纤维化的病理进程有关,提示雷米普利对舒张性心力衰竭可能有一定的治疗作用。     

替米沙坦对冠心病合并糖尿病肾病肾功能、心功能、炎症反应及血管内皮功能的影响分析

目的 探讨替米沙坦治疗冠心病(CHD)合并糖尿病肾病(DN)患者的临床效果.方法 选取88例CHD合并DN患者,采用随机数字表法分为观察组和对照组,各44例,两组患者的基础治疗均保持一致,观察组给予替米沙坦80 mg·d-1,对照组给予依那普利10 mg·d-1,疗程3个月.结果 治疗前,两组患者的血浆内皮素-1(ET-1)、一氧化氮(NO)、白细胞介素-6(IL-6)、基质金属蛋白酶-9(MMP-9)检测值均差异无统计学意义(P>0.05);治疗后,观察组患者的ET-1、IL-6、MMP-9检测值均显著的低于对照组(P<0.05),NO检测值显著的高于对照组(P<0.05);治疗前,两组患者的左室射血分数(LVEF)、左室舒张末期内径(LVEDd)均差异无统计学意义(P>0.05);治疗后,观察组患者的LVEDd值显著的低于对照组(P<0.05),LVEF值显著的高于对照组(P<0.05);治疗前,两组患者的血肌酐(Scr)、24 h尿蛋白值均差异无统计学意义(P>0.05);治疗后,观察组患者的Scr、24 h尿蛋白值均显著的低于对照组(P<0.05).结论 替米沙坦治疗CHD合并DN患者的效果优于依那普利,能够更显著的改善内皮功能、心功能及肾功能.     

替米沙坦联合复方丹参滴丸对原发性老年2级高血压患者血压及血管内皮功能的影响

目的 观察替米沙坦联合复方丹参滴丸对原发性老年2级高血压(中危组)患者血压及血管内皮功能的影响.方法 选取就诊于潍坊市人民医院高血压专家门诊以及保健三科病房的原发性老年2级高血压(中危组)患者82例,年龄65～75岁.分为复方丹参滴丸组(观察组)41例和替米沙坦组(对照组)41例,两组患者均在常规服用阿司匹林、他汀的基础上,晨起口服40 mg替米沙坦,观察组加服复方丹参滴丸每次10丸,每天3次.疗程均为4周.比较各组治疗前后患者的血压、血清一氧化氮(NO)、内皮素(ET-1)、基质金属蛋白酶9(MMP-9)、踝肱指数(ABI)的变化.结果 与治疗前相比,治疗后两组收缩压、舒张压均降低,组间比较差异有统计学意义.与治疗前相比,观察组血清NO升高,ET-1降低、MMP-9降低,ABI升高.与对照组治疗后比较,观察组经治疗后血清NO升高,ET-1下降,ABI降低.结论 替米沙坦联合复方丹参滴丸在降压的基础上,能够进一步改善血管内皮功能.     

Paediatric drug development of ramipril: reformulation,in vitro and in vivo evaluation

Ramipril is used mainly for the treatment of hypertension and to reduce incidence of fatality following heart attacks in patients who develop indications of congestive heart failure. In the paediatric population, it is used most commonly for the treatment of heart failure, hypertension in type 1 diabetes and diabetic nephropathy. Due to the lack of a suitable liquid formulation, the current study evaluates the development of a range of oral liquid formulations of ramipril along with their in vitro and in vivo absorption studies. Three different formulation development approaches were studied: solubilisation using acetic acid as a co-solvent, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) and suspension development using xanthan gum. Systematic optimisation of formulation parameters for the different strategies resulted in the development of products stable for 12 months at long-term stability conditions. In vivo evaluation showed C_max of 10.48?µg/ml for co-solvent, 13.04?µg/ml for the suspension and 29.58?µg/ml for the cyclodextrin-based ramipril solution. Interestingly, both ramipril solution (co-solvent) and the suspension showed a T_max of 2.5?h, however, cyclodextrin-based ramipril produced T_max at 0.75?h following administration. The results presented in this study provide translatable products for oral liquid ramipril which offer preferential paediatric use over existing alternatives.     

血清淀粉样蛋白A与不同糖耐量人群血管内皮功能的关系探讨

目的探讨不同糖耐量人群血清淀粉样蛋白A的水平,及与血管内皮功能的关系。方法59例患者根据OGIT试验分为3组：19例NGT、20例IGT和20例T2DM。分别检测血清淀粉样蛋白A、生化指标、肱动脉内皮依赖性舒张功能（FMD）和含服硝酸甘油后肱动脉内皮依赖性舒张功能（NID）。结果①SAA随着血糖的升高而升高,DM组的SAA较IGT组、NGT组明显升高（P〈0．01）,IGT组的SAA较NGT组升高（P〈0．05）。②FMD随着SAA的升高而下降,DM组的FMD较IGT组和NGT组明显降低（P〈0．01）,IGT组的FMD较NGT组降低（P〈0．05）。③Spearman相关分析显示SAA与FBG、HbA1c、TC均呈正相关（r值分别为0．63、0．48、0．59,P〈0．01）,与FMD呈显著负相关（r值为-0．62,P〈0．01）。结论SAA与血管内皮功能损害密切相关。     

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo‐controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45^lowCD34⁺KDR2⁺ cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)‐10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 μL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 μL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.     

Improvement of endothelial function by pitavastatin: a meta-analysis

Objective. Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD.

Methods. The authors performed a systematic review and meta-analysis of all clinical trials exploring the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.

Results. Six eligible studies comprising 7 treatment arms were selected for this meta-analysis. Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95% CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out sensitivity analysis.

Conclusion. This meta-analysis of all available clinical trials revealed a significant increase of FMD induced by pitavastatin.     

替米沙坦对2型糖尿病伴高血压患者血清细胞因子及心功能的影响

目的探讨替米沙坦对2型糖尿病伴高血压患者血清细胞因子及心功能的影响。方法将350例2型糖尿病伴高血压患者随机分为对照组与观察组,对照组150例口服依那普利,观察组170例口服替米沙坦,均治疗6个月。比较两组患者治疗前后细胞因子超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及心功能的改变。结果治疗后观察组血清hs-CRP,TNF-α和IL-6水平显著低于对照组(P<0.05),左室射血分数(EF)、左室重量指数(LVMI)及晚期血流峰值速度E/A比值显著优于对照组(P<0.05)。结论 2型糖尿病伴高血压患者血清细胞因子显著升高,替米沙坦可显著减轻机体炎性反应,改善患者心功能。     

非诺贝特对高甘油三酯血症患者胰岛素敏感性和血管内皮功能的影响

目的 观察非诺贝特对高血脂症患者代谢参数、胰岛素敏感性和血管内皮功能的影响。方法 原发高甘油三酯血症患者60例，每天予非诺贝特0．2g治疗，共12周。治疗前后分别测定甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、游离脂肪酸（FFA）、空腹血糖和胰岛素、尿酸（UA）以及血流介导的血管舒张（FMD）。结果 ①非诺贝特可显著降低TG、TC、FFA和UA，升高HDL-C（所有P〈0．01）；②非诺贝特改善胰岛素的敏感性，使胰岛素抵抗减轻6％（P〈0．05）；③非诺贝特可明显改善血流介导的血管扩张（FMD）（P〈0．01）。结论 非诺贝特不但具有调节血脂作用．还具有胰岛素增敏作用和改善内皮功能作用。胰岛素敏感性的增加与HDL水平的升高、FFA水平的降低以及内皮功能的改善有关。     

不同调脂方案对动脉硬化大鼠肝肾功能及血管内皮功能的影响

目的 探讨单用较大剂量辛伐他汀与小剂量辛伐他汀联合依折麦布对动脉硬化大鼠血管内皮功能及肝肾功能的影响.方法 将42只健康6月龄Wistar雄性大鼠完全随机分为正常对照组(n=8)、高脂对照组((n=10)、辛伐他汀低剂量组[10 mg/(kg·d),n=8]、辛伐他汀高剂量组[20 mg/(kg·d),n=8)]和辛伐他汀[10 mg/(kg·d)]联合依折麦布[5 mg/(kg·d)]组(n=8),给予相应剂量的辛伐他汀及依折麦布灌胃.分别于实验第8周末眼静脉丛采血及第12周末心脏采血后测定各组大鼠TC、LDL-C、HDL-C、TG、ALT、AST、血清肌酐(Scr)、BUN、尿酸、尿蛋白、尿肌酐(Ucr)、血清肌酐清除率(Ccr)、C反应蛋白(CRP)、可溶性血栓调节蛋白(sTM)和可溶性细胞间黏附因子1(sICAM-1)水平及尿蛋白浓度,并计算肾指数.结果 ①辛伐他汀低剂量组、高剂量组,辛伐他汀联合依折麦布组较高脂对照组TC、LDL-C、TG、ALT、AST、BUN、尿酸、尿蛋白、CRP、sTM、sICAM-1水平明显降低(P＜0.01),HDL-C及Ccr水平升高,其中辛伐他汀高剂量组肾功能明显改善[实验12周末血Scr:(2.00±0.47) ml/min比(0.55±0.12) ml/min,BUN:(5.25±0.50) mmol/L比(7.82±0.25) mmol/L,尿酸:(81±17) μmol/L比(142±13) μmol/L,尿蛋白:(1.98±0.18) g/L比(2.89±0.32) g/L]、sTM、sICAM-1水平明显降低[实验12周末sTM:(165±26) g/L比(279±30) g/L,sICAM-1:(20.1±3.2)g/L比(48.1±6.4)g/L],辛伐他汀联合依折麦布组血脂及肝功能明显改善.②光镜下:各处理组肾小球体积小,系膜细胞增生减轻,且均以辛伐他汀高剂量组改善明显.结论 ①单用较大剂量辛伐他汀与小剂量辛伐他汀联合依折麦布相比,能更好降低BUN、尿酸、尿蛋白、sTM和sICAM-1水平,降低肾指数,提高Ccr和HDL-C水平,改善肾小球形态,从而起到改善肾功能及血管内皮功能的作用.②小剂量辛伐他汀联合依折麦布较单用大剂量辛伐他汀更能显著降低TC、LDL-C和CRP水平,且不增加血清转氨酶水平,有效降脂的同时不增加肝功能损害.     

Alcohol and endothelial function: a brief review

1. In spite of the dose-related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke. 2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelium-dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium-mediated vasodilatation and may even result in augmentation of such responses. 3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow-mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short-term interventions to reduce alcohol intake have had no effect to either improve or impair FMD. 4. Further studies in humans assessing acute and longer term dose-related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease.     

Assessment of endothelial function in atrial fibrillation: utility of peripheral arterial tonometry

Endothelial function is an independent predictor of adverse cardiovascular outcomes. The evaluation of endothelial function via changes in vessel diameter or blood flow may be inaccurate during atrial fibrillation (AF) because of non-uniform stroke volumes. Using peripheral arterial tonometry, 50 patients with AF (25 in AF, 25 in sinus rhythm) had digital pulse amplitudes assessed at baseline and during reactive hyperaemia. Hyperaemic responses were compared over varying measurement durations (5, 10 and 15beats; 30s; and 1-10min) to determine optimal measurement duration. Endothelial responses were significantly decreased (indicating endothelial dysfunction) in patients in AF compared with patients in sinus rhythm (1.48±0.60 vs 2.05±1.13, respectively; P=0.03). Beat-to-beat pulse amplitude was highly variable during AF; although coefficients of variation (CV) for short measurement durations were large, these decreased with longer measurement durations. Bland-Altman plots revealed that limits of agreement for short measurement durations were poor. Limits of agreement became consistently narrower when measurement durations of at least 1min were used. In contrast, limits of agreement and CV for short measurement durations during sinus rhythm were significantly narrower and smaller, respectively, than during AF over similar measurement durations. Pulse amplitudes are highly variable owing to the non-uniform stroke volumes in AF. Our results suggest that methods of determining endothelial function via vessel diameters or blood flow during reactive hyperaemia should use measurement durations of at least 1min to ensure accurate and reproducible results.     

Effect of naproxen and acetaminophen on blood pressure lowering by ramipril,valsartan and aliskiren in hypertensive patients

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for reducing pain and other symptoms in osteoarthritis (OA). NSAIDs have been associated with an increase in blood pressure (BP) in both normotensive and hypertensive individuals and a blunting effect on various anti-hypertensive medications. Acetaminophen effects on anti-hypertensive treatment, instead, are still a matter of debate.

Objectives: To assess the effect of naproxen versus acetaminophen on ramipril, valsartan and aliskiren therapy in hypertensive patients with OA in a double-blind, cross-over study, by measuring clinic, ambulatory BP and heart rate (HR).

Results: One hundred seventy four patients were randomly treated with ramipril, valsartan or aliskiren for 8 weeks and 135 patients with normalized BP were randomized to receive naproxen or acetaminophen for 2 weeks. Naproxen significantly increased clinic and ambulatory systolic/diastolic BP (SBP/DBP) values in patients treated with ramipril (p < 0.01) or valsartan (p < 0.05), but did not affect aliskiren effects. Also acetaminophen slightly but significantly affected clinic and ambulatory SBP/DBP in all three groups and, surprisingly, it also produced a slight increase in HR (+3.1, +3.3 and +3.4 b/min day-time HR values, for ramipril, valsartan and aliskiren, respectively; p < 0.05).

Conclusions: Both naproxen and acetaminophen can affect anti-hypertensive therapy with ramipril, valsartan or aliskiren with a different extent. When acetaminophen is chosen for OA management in subjects with hypertension, patients should be evaluated as carefully as when traditional NSAIDs are given.     

动物勃起模型研究抗雄激素对勃起功能的影响

目的　应用阿朴吗啡 (APO)诱导大鼠阴茎勃起模型 ,探讨抗雄激素对阴茎勃起功能的影响及其可能机制。方法　SD雄性成年大鼠随机分为 3组 ,伪手术组、睾丸切除组及非手术组。用已建立的APO诱导大鼠阴茎勃起模型观察睾丸切除、睾酮恢复及抗雄激素氟他胺对阴茎勃起和呵欠反应的影响。结果　各剂量APO(2 0、40、80、160 μg kg)均能引起伪手术组大鼠出现阴茎勃起和呵欠反应 ,但不能引起睾丸切除组大鼠出现阴茎勃起反应 ,睾丸切除组呵欠次数与伪手术组比较也显著减少 (P <0 0 5 )。给予睾酮后阴茎勃起功能部分恢复 ,呵欠次数恢复到伪手术组水平。氟他胺 (5 0mg kg)能引起阴茎勃起次数显著减少 (P <0 0 5 ) ,但对呵欠次数无明显影响。结论　阴茎勃起功能是雄激素依赖的 ,抗雄激素氟他胺能引起勃起功能障碍 ,APO诱导大鼠阴茎勃起模型可以用来初步筛选抗雄激素