Hydrogen water consumption prevents osteopenia in ovariectomized rats

Background and Purpose

Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy-induced osteoporosis.

Experimental Approach

Ovariectomized rats were fed with HW (1.3 ± 0.2 mg·L⁻¹) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone.

Key Results

HW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL-6 and TNF-α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats.

Conclusions and Implications

HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.     

Alleviation of ovariectomy-induced osteoporosis in rats by <Emphasis Type="Italic">Panax notoginseng</Emphasis> saponins

To examine the effects of Panax notoginseng saponins (PNS), the main active components of Panax notoginseng, on ovariectomy-induced osteoporosis in rats. A total of 72 six-month-old female rats were randomly assigned to sham-operated group and five ovariectomized (OVX) groups: OVX with distilled water (5 ml/kg/day, p.o.), OVX with graded doses of PNS (75, 150, 300 mg/kg/day, p.o.), and OVX with nilestriol (1 mg/kg/week, p.o.). Animals were sacrificed after a 13-week treatment course. Compared with the OVX group, PNS administration prevented OVX-induced decrease in bone mineral density (BMD) of lumbar vertebrae and total femur, and significantly increased bone structural biomechanical properties. Improvements of BMD and biomechanical properties were accompanied by the beneficial changes of PNS on trabecular microarchitecture in the tibial metaphysis. PNS at the highest dose significantly prevent decrease in trabecular bone volume over bone total volume, trabecular number, trabecular thickness, connectivity density, and increase in trabecular separation and structure model index in OVX rats. The bone-modulating effects of PNS may be due to the increased bone formation and decreased bone resorption, as was evidenced by the elevated level of serum alkaline phosphatase and decreased level of urinary deoxypyridinoline. PNS treatment is able to enhance BMD, bone strength, and prevent the deterioration of trabecular microarchitecture without hyperplastic effect on uterus. Therefore, PNS might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.     

白藜芦醇对去卵巢大鼠股骨骨保护素及核因子κB受体活化子配体表达的影响

目的：观察白藜芦醇对去卵巢大鼠股骨骨保护素（OPG）及核因子κB受体活化子配体（RANKL）表达的影响。方法：健康3月龄雌性SD大鼠48只，按体重随机分为6组：假手术组（SHAM）、单纯卵巢切除组（OVX）、17β-雌二醇组（ERT，0．1mg·kg^-1·d^-1）。低、中、高剂量白藜芦醇组（RL、RM、RH，每天分别给予10、20、40mg／kg白藜芦醇）。除假手术组外其余各组均切除双侧卵巢。术后1周开始给药，给药8周后处死所有大鼠，测定股骨骨密度（BMD）及骨生物力学性能：弹性模量（ELASTIC）、刚度（STIFFNESS）、最大应力（M-STRESS）最大承载力（M-LORD）。用免疫组织化学染色方法观察股骨OPG、RANKL的表达。结果：与OVX组比较，20、40mg·kg^-1·d^-1白藜芦醇均能上调股骨OPG表达（P〈0．05）。与OVX组比较，20、40mg·kg^-1·d^-1白藜芦醇均下调RANKL的表达，改善股骨骨密度及生物力学性能（P〈0．05）。结论：白藜芦醇在体内可上调骨组织中OPG的表达，下调RANKL的表达，这可能是其改善股骨骨密度及生物力学性能的作用机制。     

Modulation of matrix metalloproteinase-1, its tissue inhibitor, and nuclear factor-kappa B by losartan in hypercholesterolemic rabbits

Upregulation of angiotensin II receptor, may be involved in the initiation and progression of atherosclerosis. To examine the contribution of AT1 receptor in the expression of matrix metalloproteinase-1 (MMP-1) and its tissue inhibitor (TIMP-2) in lipid-deposited arterial tissues, New Zealand white rabbits were given high-cholesterol chow (with losartan 25 mg/d or vehicle) for 10 weeks. Losartan reduced the areas of sudanophilia in the aorta of rabbits fed high-cholesterol diet (p < 0.01 vs. control). Losartan also significantly decreased the enhanced mRNA expression of MMP-1 and TIMP-2 in aortas of rabbits with high-cholesterol diet. Losartan-treated rabbits revealed a reduction in immunohistochemical expression of MMP-1, whereas TIMP-2 expression became localized to the intima. In addition, losartan treatment reduced the activation of NF-kappa B by inhibiting the degradation of its inhibitor I kappa-B alpha. These observations demonstrate that AT1 receptor blockade with losartan reduces lipid deposition and exerts potent inhibitory effects on NF-kappa B activation and modulates the expression of MMP-1 and TIMP-2 in hypercholesterolemic rabbits.     

Use of losartan in diabetic patients in the primary care setting: review of the results in LIFE and RENAAL

SUMMARY

Objective: To review outcomes of diabetic patients treated with losartan in two recent randomized, double-blind, clinical trials and compare outcomes to similar studies in diabetics.

Methods: The Reduction in ENdpoints with the Angiotensin II Antagonist Losartan (RENAAL) study recruited 1513 patients with type 2 diabetes and nephropathy. The Losartan Intervention For Endpoint reduction (LIFE) study recruited 9193 hypertensive patients with left ventricular hypertrophy (LVH) including 1195 with diabetes mellitus. The maximum losartan dose in both studies was 100?mg daily. All study patients could receive additional antihypertensive medications, excluding angiotensin converting enzyme inhibitors (ACEIs) and other angiotensin receptor blockers (ARBs), if blood pressures (BP) < 140/90?mmHg were not achieved. In RENAAL, the control group received placebo whereas in LIFE, controls received atenolol. BP reductions were comparable in the treatment and control groups of both studies. In RENAAL, the primary outcome was the composite of doubling of serum creatinine, end-stage renal disease, or death. In LIFE, the primary composite outcome was cardiovascular death and non-fatal myocardial infarction or stroke.

Results: In RENAAL, losartan reduced the primary composite end-point 16% (?p = 0.02) and the incidence of end-stage renal disease (ESRD) 28% (?p = 0.002). In LIFE, the primary composite endpoint among diabetics was reduced 24% (?p = 0.03), cardiovascular mortality was reduced 37% (?p = 0.03) and total mortality was reduced 39% (?p = 0.002).

Discussion: In diabetic patients with nephropathy, losartan reduces progression to end-stage renal disease. In hypertensive diabetic patients with LVH, losartan reduces cardiovascular morbidity and mortality and total mortality. Angiotensin receptor blockade with losartan appears to confer benefits beyond BP reduction in diabetic patients at high-risk for cardiovascular and renal events.     

Effects of flaxseed lignan and oil on bone health of breast-tumor-bearing mice treated with or without tamoxifen

Previous studies showed that flaxseed lignan (secoisolariciresinol diglucoside, SDG) and oil (FO) inhibit established breast tumor growth in athymic mice with or without tamoxifen (TAM) treatment. TAM was found to increase bone mineral content (BMC) and density (BMD) in breast cancer patients. It is not known whether SDG or FO alone or combined with TAM affects bone health. Hence, the effects of SDG and FO, alone or in combination, on BMC, BMD, and biomechanical bone strength in ovariectomized athymic mice with established human breast tumors (MCF-7) treated with or without TAM were studied. In a factorial design, mice were divided into four non-TAM and four TAM groups. Each group consisted of mice fed a basal diet (BD), SDG (1 g/kg), FO (38.5 g/kg) or SDG + FO (combination) diets. The TAM group had TAM implants that provide a 5-mg TAM dose released over 60 d. TAM exerted an overall significant effect in increasing BMC, BMD, and biomechanical strength in femurs and lumbar vertebra. Without TAM treatment, SDG produced significant lower femur BMD (6%) while FO produced lower vertebrae BMC (8%) and BMD (6%). With TAM treatment, SDG and FO did not exert an effect on BMC and BMD at the femur or vertebra. SDG and FO produced no marked effect on biomechanical bone strength with or without TAM treatment. In conclusion, FS components did not significantly attenuate the positive effects on bone induced by TAM in this model system, indicating no apparent adverse effects on bone health.     

氯沙坦对造血祖细胞优势扩增影响的研究

目的探讨氯沙坦[血管紧张素Ⅱ的1型受体(AT1R)拮抗剂]对不同系别造血祖细胞分化的影响及其分子机制。方法由正常脐血分离出的单个核细胞在含不同浓度氯沙坦培养基中悬浮培养,然后转到半固体培养基,观察并计数红系爆式集落形成单位(BFU-E)和粒-单系集落形成单位(CFU-GM),流式细胞仪检测红系和粒系所占比例。巢式反转录聚合酶链反应(nested-RT-PCR)检测AT1R基因的mRNA表达。结果①红系祖细胞在悬浮培养6、9d时检测到AT1R的表达,氯沙坦可阻断此效应。②氯沙坦抑制红系分化,促进粒系分化,且呈浓度依赖性,集落计数结果示其量-效关系为Y=100.125-22.496lgX(X:氯沙坦浓度;Y:红系集落数);Y=220.594+21.882lgX(X:氯沙坦浓度;Y:粒系集落数);流式细胞仪检测示其量-效关系为Y=4296.032-435.335lgX(X:氯沙坦浓度;Y:红系细胞数);Y=5430.975+643.853lgX(X:氯沙坦浓度;Y:粒系细胞数)。③氯沙坦对红系和粒系作用的最适浓度为20nmol/ml。结论氯沙坦能下调AT1R的表达。通过阻断血管紧张素Ⅱ与AT1R的结合,氯沙坦能抑制红系分化,进而使得粒系分化增加。氯沙坦对红系和粒系的作用呈浓度依赖性。     

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure

Losartan (COZAAR) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT(1)) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT(1) receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT(1) receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT(1) receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT(1) receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT(1) receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.     

The role of angiotensin antagonism in stroke prevention in patients with hypertension: focus on losartan

Summary

Optimal management of hypertension has been shown to reduce the risk of stroke. In recent years, newer classes of antihypertensive such as the angiotensin II (Ang II) antagonists have become available. Results from the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study suggest the utility of this particular Ang II antagonist in stroke prevention. Treatment with a losartan-based regimen or an atenolol-based regimen produced similar reductions in blood pressure during almost 5 years of follow up. Losartan, however, reduced the risk of stroke by 25% compared with atenolol (p = 0.001). For a subgroup of patients with isolated systolic hypertension, losartan reduced the risk of stroke by 40% (p = 0.02). As well as blocking the Ang II type 1 receptor, losartan also acts as an antagonist at the thromboxane A₂ receptor and has uricosuric effects, which may provide additional mechanisms by which losartan provides protective benefits beyond its antihypertensive action. The relevance of these molecular properties of losartan over other Ang II antagonists is further supported by comparison of the outcomes obtained in clinical trials employing two other Ang II antagonists, valsartan and candesartan.     

Biphasic effects of losartan potassium on immobility in mice

The effects of losartan potassium, an angiotensin AT(1) receptor blocker on immobility in forced swim test have been studied. Effect of losartan potassium, nortriptyline HCl, fluoxetine HCl and reserpine per se and in combination on forced swimming-induced immobility in mice have also been studied. In mice, losartan potassium elicits biphasic responses i.e. positive responses at lower doses (0.1, 1.0 and 5 mg/kg, i.p.) in the forced swim test, a test of potential antidepressant activity and vice versa at higher dose (20 and 100 mg/kg, i.p.). In chronic studies, enhancement in immobility was observed for losartan potassium (3 and 30 mg/kg, p.o., 21 days). In acute combination studies, losartan potassium (1 and 5 mg/kg) significantly reversed the reserpine-induced immobility, but vice versa at 100 mg/kg. Losartan potassium (0.1 and 5 mg/kg) potentiate antidepressant activity of nortriptyline (30 mg/kg, i.p.) in mice, but vice versa at 100 mg/kg. Likewise, Losartan potassium (100 mg/kg), significantly reversed antidepressant activity of fluoxetine HCl, but at 0.1 and 5 mg/kg, failed to modify fluoxetine HCl induced immobility. The obtained biphasic effect of losartan potassium on immobility in mice might be due to inhibitory effect on AT(1) receptor at lower dose and pronounced effect on AT(2) receptor at higher dose (large concentrations of losartan potassium can displace Angiotensin II (Ang II) from its AT(1) receptor to AT(2) receptor.     

Exposure to tobacco smoke increases bone loss in spontaneously hypertensive rats

Abstract

Purpose: To define if exposure to tobacco smoke (TS) could induce reduction of bone mass and impairment of bone architecture, features observed in osteoporosis in normotensive rats and the influence of TS exposure on the osteoporotic features exhibited in the spontaneously hypertensive (SH) rats.

Methods: Normotensive Wistar Kyoto (WKY) and SH rats were exposed to filtered air or TS for 8?weeks, then their proximal femurs were extracted for micro-computed tomography (micro-CT) assessment, histological and immune-histological examinations to quantify the adverse influence of TS exposure on the bone mass and density, as well as bone architecture.

Results: We found that TS exposure not only induced significant decreases in bone mineral density (BMD), bone volume (BV), cortical and trabecular thickness (Ct.Th and Tb.Th), trabecular surface area (Tb.Ar), expression of hypoxia-inducible factor-1α (HIF-1α) in the trabecular marrow, delayed ossification of cartilage, as well as statistical increases in trabecular separation (Tb.SP) and the number of trabecular marrow adipocytes in both WKY and SH rats, but also exacerbated multiple features of osteoporosis exhibited in SH rats, including decreased BMD, Ct.Th, Tb.Ar, HIF-1α expression, delayed cartilage ossification, and increased Tb.SP.

Conclusions: Our results show that TS exposure can reduce bone mass and impair bone architecture and exacerbate multiple features of osteoporosis exhibited in SH rats.     

Compression Shear Strength and Tableting Behavior of Microcrystalline Cellulose Agglomerates Modulated by a Solution Binder (Polyethylene Glycol)

Purpose. To investigate the possibility of modulating the compression shear strength of agglomerates by the incorporation of a solution binder and to study the subsequent effect on the deformation behavior and tablet forming ability of the agglomerates. Method. Various concentrations (0.5 to 10%) of polyethylene glycol were incorporated as a solution binder into microcrystalline cellulose agglomerates of different porosity (10 and 20%) and the shear strength of the agglomerates, as evaluated by the 1/b value of the Kawakita equation, and the permeability to air and tensile strength of tablets formed from them were determined. Results. Increased agglomerate porosity and concentration of polyethylene glycol reduced the 1/b values, which led to the formation of tablets with a lower permeability. A decreased tablet permeability corresponded to an increased tablet tensile strength except that the highest binder content was associated with a drop in the tablet tensile strength. Conclusions. The solution binder reduced the agglomerate shear strength, which was expressed as an increased degree of agglomerate deformation during compression. The latter seemed to be controlled by both agglomerate porosity and shear strength. The main role of the solution binder in improving the agglomerate compactability was to increase the degree of deformation of agglomerates during compression.     

穿山龙总皂苷对去卵巢模型大鼠骨质疏松的改善作用

目的探讨穿山龙总皂苷对去卵巢模型大鼠骨质疏松的改善作用。方法将80只SD大鼠分为模型组(等体积0.9%氯化钠溶液)、17β-雌二醇组(1.6 g/kg)和穿山龙总皂苷低、高剂量组(2 g/kg和4 g/kg),各20只。麻醉大鼠,结扎输卵管,切除双侧卵巢,以复制去卵巢大鼠模型。建模成功后,各组大鼠灌胃给予相应药物(10 mL/kg)或等体积0.9%氯化钠溶液,每天1次,持续8周。另取20只大鼠作为正常对照组(等体积0.9%氯化钠溶液)。检测大鼠股骨骨密度(BMD)及股骨弹性模量、刚度、最大应力、最大承载力;苏木素-伊红(HE)染色观察大鼠股骨病理形态学;采用逆转录聚合酶链式反应(RT-PCR)法和Western blot法检测大鼠股骨组织Wnt、细胞外调节蛋白激酶(ERK)mRNA和蛋白表达水平。结果与模型组比较,17β-雌二醇组和穿山龙总皂苷低、高剂量组大鼠股骨BMD、弹性模量、刚度、最大应力、最大承载力,以及股骨组织Wnt、ERK mRNA和蛋白表达水平均显著升高(P <0.05);股骨远端小梁的形态结构改善,股骨小梁密度增加,空骨腔减少,小梁排列有序。结论穿山龙总皂苷能增加...     

来氟米特联合氯沙坦钾对糖尿病肾病患者肾小球足细胞的影响

目的 探讨来氟米特联合氯沙坦钾对糖尿病肾病（DN）患者肾小球足细胞的影响。方法 将60例DN患者随机分为对照组与治疗组各30例，对照组予氯沙坦钾治疗，50 mg/次口服，1次/d；治疗组在对照组基础上给予来氟米特治疗，前3 d剂量为50 mg/次，1次/d，之后减量至20 mg/次，1次/d。两组疗程均为6周。分别在治疗前后检测血肌酐（Scr）、尿素氮（BUN）、24 h蛋白尿定量、尿足细胞数及其标志蛋白（PCX）。结果 治疗前，两组Scr、BUN、24 h蛋白尿定量均无统计学差异；治疗后，两组Scr、BUN、24 h蛋白尿定量均较治疗前明显下降，同组治疗前后比较差异有统计学意义（P<0.05）；且治疗组以上指标明显低于对照组，差异有统计学意义（P<0.05）。治疗前，两组尿足细胞数和PCX水平比较，差异无统计学意义；治疗后，两组尿足细胞数和PCX水平较治疗前明显降低，同组治疗前后比较差异有统计学意义（P<0.05）；且治疗组明显低于对照组，差异有统计学意义（P<0.05）。治疗组总有效率为93.3%，明显优于对照组的73.3%，差异有统计学意义（P<0.05）。结论 来氟米特联合氯沙坦钾治疗DN的疗效较好，可有效减少肾小球足细胞的损伤。     

Pharmacokinetics and blood pressure response of losartan in end-stage renal disease

BACKGROUND: Losartan is a selective angiotensin AT1 receptor antagonist currently employed in the management of essential hypertension. This compound is in common use in populations with renal failure and end-stage renal disease (ESRD). OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of losartan in patients with ESRD in order to establish administration guidelines. METHODS: Patients were administered losartan 100 mg/day for 7 days, and after the seventh and final dose pharmacokinetic parameters were determined for both losartan and its active metabolite E-3174. During the study, the haemodialytic clearances of losartan and E-3174 were measured during a standard 4-hour dialysis session. Neurohumoral and biochemical changes were assessed during losartan administration. RESULTS: The pharmacokinetics of losartan and E-3174 in haemodialysis patients did not alter to a clinically significant level. Losartan administration was accompanied by a decline in plasma aldosterone level as well as by an increase in plasma renin activity. Losartan administration resulted in a decline in plasma uric acid level, despite the fact that the study participants had no residual renal function. Losartan and E-3174 were not dialysable. CONCLUSIONS: The pharmacokinetics of losartan and E-3174 are minimally altered in ESRD; thus, dosage adjustment is not required in the presence of advanced dialysis-dependent renal failure. In addition, postdialysis supplementation is not required for losartan because of the negligible dialysability of losartan and E-3174.     

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats

Abstract

Context: Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats.

Objective: This study investigates the effect of RDE against bone loss induced by simulated microgravity.

Materials and methods: A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague–Dawley rats were divided into four groups (n?=?6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0?mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500?mg/kg/d). RDE or ALN was administrated orally for 4 weeks.

Results: Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index.

Discussion and conclusion: RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.     

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure

Losartan (COZAARΟχιρχ^?) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT₁) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT₁ receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT₁ receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT₁ receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT₁ receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT₁ receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.     

Losartan: a review of its use, with special focus on elderly patients

Losartan is an orally active, nonpeptide, selective angiotensin subtype 1 (AT1) receptor antagonist. It provides a more specific and complete blockade of the actions of angiotensin II than renin or ACE inhibitors. Short term (up to 12 weeks' duration) clinical trials have shown losartan to be as effective at lowering blood pressure (BP) [causes a decrease in BP < or = 26/20 mm Hg] in elderly patients with hypertension as recommended dosages of captopril, atenolol, enalapril, felodipine and nifedipine. In patients with isolated systolic hypertension (ISH) the efficacy of losartan was similar to that of atenolol. The addition of hydrochlorothiazide to losartan therapy provides greater antihypertensive efficacy, equivalent to that seen with captopril plus hydrochlorothiazide. Preliminary evidence also indicates that losartan therapy contributes to the regression of left ventricular hypertrophy associated with chronic hypertension. Exercise capacity is increased by losartan in patients with either asymptomatic or symptomatic heart failure. Results from the Losartan Heart Failure Survival or ELITE II (Evaluation of Losartan in the Elderly II) study indicate that there was no statistically significant difference between losartan and captopril in reducing overall deaths or in reducing sudden cardiac death and/or resuscitated cardiac arrest in patients with heart failure. Other than ELITE II, little conclusive long term mortality and morbidity data exist for losartan. Additional long term trials to evaluate the survival benefits of losartan in elderly patients with hypertension, renal disease or after an acute myocardial infarction are currently in progress. In elderly patients with hypertension, the incidence of treatment-related adverse events associated with once daily losartan (alone or in combination with hydrochlorothiazide) [19 to 27%] was similar to felodipine (23%) and nifedipine (21%), however, losartan tended to be better tolerated than captopril (11 vs 16%). Losartan was also better tolerated than atenolol in patients with ISH (10.4 vs 23%). In patients with heart failure the renal tolerability of losartan was similar to that of captopril, but losartan was associated with a lower withdrawal rate because of adverse events. No dosage adjustment is required in elderly or in patients with mild to moderate renal dysfunction, and the risk of first-dose hypotension is low. Conclusions: comparative data have shown losartan to be as effective as other antihypertensive agents in the treatment of elderly patients with hypertension. Treatment with losartan is therefore an option for first-line therapy in all patients with hypertension, particularly those who are not well managed with or who are intolerant of their current therapy. Morbidity and mortality data from the Losartan Heart Failure Survival (ELITE II) study show that losartan has potential in the treatment of heart failure.     

洛沙坦抗高血压及左室肥厚的疗效观察

目的 :观察血管紧张素 受体拮抗剂—洛沙坦的降压效果及对高血压病合并左室肥厚的影响。方法 :4 6例合并左室肥厚的 期高血压病患者服用洛沙坦 5 0 mg/ d,观察其血压的变化及治疗前和 6个月后左室质量 (L VM)。结果 :用洛沙坦后 4 d～ 6d血压开始下降 ,2周血压趋向正常 ,4周血压继续缓慢下降 ,6周时达到最大降压效果。 L VM在 12周时无明显变化。 2 4周表现轻度 L VM减少。结论 :洛沙坦是抗高血压的一个有效治疗药物 ,对左心室肥厚有轻度逆转作用     

Losartan: a review of its use in stroke risk reduction in patients with hypertension and left ventricular hypertrophy

Losartan (Cozaar) is an angiotensin AT1 receptor antagonist. It is approved in numerous countries for the treatment of hypertension and has been approved in the UK, the US and several European countries for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan is recommended for use alone or with hydrochlorothiazide, but it can also be administered with other antihypertensive medications. In patients with hypertension, losartan effectively lowers blood pressure and also leads to regression of LVH. In the large, well designed LIFE (Losartan Intervention For Endpoint reduction in hypertension) study in patients with hypertension and LVH, losartan was more effective than atenolol in reducing the composite primary endpoint of cardiovascular (CV) mortality, stroke or myocardial infarction (MI). This was mainly due to a significant 25% reduction in the risk of stroke in the losartan group. Losartan recipients also had a significantly lower incidence of new-onset diabetes mellitus compared with atenolol recipients. Similar benefits were observed in several patient subgroups from the LIFE study, but not in the subgroup of Black patients. Losartan is well tolerated and is a cost effective alternative to atenolol in the setting of stroke reduction. Comparative data on clinical outcomes in hypertensive patients for losartan versus other antihypertensive agents would be of interest. Nonetheless, in addition to its established antihypertensive and end organ effects, the LIFE study indicates that, with the possible exception of Black patients, losartan can reduce the risk of stroke in patients with hypertension and LVH.