科素亚对高血压鼠肾小球系膜扩张的抑制作用

目的 探讨新一代降压药血管紧张素Ⅱ受体拮抗剂对肾脏(肾小球)的保护作用。方法 由高血压组(SHR)和正常对照血压组(WKY鼠)组成,其中SHR组再分为治疗组[予科素亚20mg/(kg·d)]和非治疗组,分别于三月龄和八月龄测量鼠尾动脉压、及电子显微镜下有关病理指标。结果 与正常血压对照组比较,高血压鼠系膜细胞体密度明显增大,显示增生较前者活跃,可见较多的电子致密物聚积并使整个系膜区体密度扩大。而经科素亚治疗后系膜细胞的过度增生肥大能被有效地抑制,系膜区体密度及细胞外基质较非治疗组明显减少或减少。结论 科素亚在降低动脉压同时,有效地保护了肾脏,抑制高血压肾小球系膜细胞增生及系膜区扩张。     

Efficacy and safety of DALI-LDL-apheresis in two patients treated with the angiotensin II-receptor 1 antagonist losartan

Direct adsorption of lipids (DALI) is the first low-density lipoprotein (LDL)-apheresis technique capable of adsorbing LDL and lipoprotein (a) directly from whole blood. The adsorber consists of negatively charged polyacrylate ligands linked to a Eupergit matrix. Negatively charged ligands give rise to activation of bradykinin, which is rapidly degraded by the angiotensin converting enzyme (ACE). Thus, angiotensin converting enzyme inhibitors are contraindicated in DALI-LDL-apheresis. This is the first paper to describe the efficacy and safety of DALI-LDL-apheresis in patients treated with 50 mg of the angiotensin II-receptor 1 antagonist (ARA) losartan. Two hypercholesterolemic patients were treated for 79 patient months with weekly or biweekly DALI sessions (N = 221 sessions). Approximately 1.4 patient blood volumes were treated per session. Acute reductions of LDL-cholesterol (63%) and lipoprotein (a) (62%) exceeded 60% and laboratory safety parameters remained in the apheresis typical range. Mean bradykinin plasma levels peaked in the efferent line post-adsorber at 1000 mL of treated blood volume; 467 fmol/mL (N = 6 sessions) in the ARA-treated patients and 671 fmol/mL (N = 9 sessions) in a control group of three DALI patients without ARA medication (P = 0.69, n.s.). Clinically, the DALI sessions for the ARA-treated patients were completely uneventful and blood pressure was not significantly different in the two groups. In summary, according to this retrospective pilot study, DALI-LDL-apheresis was shown for the first time to be safe and effective in patients on ARA medication.     

Bradykinin May Not Be Involved in Improvement of Insulin Resistance by Angiotensin Converting Enzyme Inhibitor

We have previously demonstrated that captopril ameliorates glucose intolerance by partially preventing the reduction in postprandial skeletal muscle blood flow. The present study was designed to clarify the mechanism by which ACE inhibitors affect glucose metabolism in fructose (FRU)-fed Wistar rats with hypertension, glucose intolerance and hyperinsulinermia. Eight-week-old male rats (n=51) were divided into six groups. Controls were given a normal chow, while fructose-rich (55%) chow was administered to the remainder for eight weeks. The different groups were administered alacepril (ALA, 30 mg/kg/day) with or without a continuous infusion of Hoe 140, a kinin B₂ receptor antagonist (150 μ/kg/day), Hoe 140 alone or TCV-116 (1 mg/kg/day), an angiotensin II receptor antagonist, alone. After measuring the body weight and systolic bolld pressure (BP), steady-state plasma glucose (SSPG) levels were determined. FRU significantly increased BP from 141 mmHg in controls to 156 mmHg. ALA with or without Hoe 140 decreased BP to 124 mmHg or 117 mmHg, respectively, but Hoe 140 alone did not affect BP. TCV-116 also decreased BP to 11 6 mmHg. The SSPG levels increased from 7.58 mM in controls to 8.98 mM in FRU-fed rats. This was lowered with both ALA and TCV-116. Hoe 140 alone, however, did not affect SSPG levels. Hoe 140 did not show any effects on ALA-induced improvement of SSPG. These results suggest that the improvement in glucose tolerance observed with ACE inhibitors is not due to the kinins, and angiotensin II receptor antagonists also improve insulin sensitivity.     

CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis

The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on indomethacin-induced small intestinal injury in rats. Single administration of indomethacin provoked severe inflammatory lesions in the small intestine. The levels of thiobarbituric acid-reactive substances (TBARS), myeloperoxidase (MPO) activities and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in the indomethacin-treated group compared with the sham group. In addition, the angiotensin II type I receptor was increased in the small intestine after the administration of indomethacin. The development of intestinal lesions in response to indomethacin was prevented by pretreatment with CV-11974 together with significant suppression of the increased level of TBARS, MPO activities and CINC-1. These results indicate that CV-11974 protected against the small intestinal damage elicited by indomethacin, which suggests that angiotensin II/AT1 receptor interaction is involved in the pathogenesis of the intestinal inflammation associated with oxidative stress.     

Cardioprotective Effect of Angiotensin n Receptor Antagonist on Perfused Ischemic Reperfusion Injury of Whole Isolated Rat Hearts

Objectives Investigated the cardioprotective and mechanisms of losartan on whole isolated ischemic reperfused rat heart. Methods Langendorff perfused systems was used to investigate losartan effect on whole isolated rat hearts in CPK, LDH, MDA, SOD, ang II and arrhythmia. Results Losartan decreased incidence of arrhythmia, improved atrial ventricular block recovery in reperfu-sion period, during ischemic period, CPK and LDH in I/R group increased significantly compared with control group, 51. 33±27. 02 vs 22. 42 ± 13. 33, 31. 80 ±4.56 vs 22. 28 ± 15. 96, respectively, but greatly decreased in losartan group compared with I/R group, 23. 90±21.74 vs 51. 33 ±27. 02 and 11. 50 ±13. 20 vs 31. 80 ±4. 56, respectively. During reperfusion period CPK, LDH increased significantly in I/R group compared with control group, 49. 11 ± 20. 63 vs 12. 14 ±5.92 and 28. 70±4. 69 vs 23. 10±21. 38, respectively, but decreased greatly in losartan group compared with I/R group, 39. 40 ± 9. 60 vs 49. 11 ± 20.63 an     

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.     

Cardioprotective Effects of Angiotensin II Type 1 Receptor Blockade with Olmesartan on Reperfusion Injury in a Rat Myocardial Ischemia‐Reperfusion Model

We determined the effects of olmesartan on infarct size and cardiac function in a rat ischemia/reperfusion model. Rats underwent 30 min of left coronary artery (CA) occlusion followed by 2 h of reperfusion. In protocol 1, the rats received (by i.v.) 1 mL of vehicle at 10 min after CA occlusion (Group 1, n = 15); olmesartan (0.3 mg/kg) at 10 min after CA occlusion (Group 2, n = 15); 1 mL of vehicle at 5 min before CA reperfusion (Group 3, n = 15); or olmesartan (0.3 mg/kg) 5 min before CA reperfusion (Group 4, n = 15). In protocol 2, the rats received (by i.v.) 1 mL of vehicle at 5 min before CA reperfusion (Group 5, n = 21); or olmesartan (3 mg/kg) at 5 min before CA reperfusion (Group 6, n = 21). Systemic hemodynamics, left ventricular (LV) function, LV ischemic risk zone, no‐reflow zone, and infarct size were determined. In protocol 1, olmesartan (0.3 mg/kg) did not affect blood pressure (BP), heart rate, LV ± dp/dt or LV fractional shortening during the experimental procedure, and did not alter no‐reflow or infarct size. In protocol 2, olmesartan (3 mg/kg) significantly reduced infarct size to 21.7 ± 4.1% from 34.3 ± 4.1% of risk zone in the vehicle group (P= 0.035), but did not alter the no‐reflow size. Prior to CA reperfusion, olmesartan (3 mg/kg) significantly reduced mean BP by 22% and LV ±dp/dt, but did not affect heart rate. At 2 h after reperfusion, olmesartan significantly decreased heart rate by 21%, mean BP by 14%, and significantly increased LV fractional shortening from 54.1 ± 1.4% to 61.3 ± 1.6% (P= 0.0018). Olmesartan significantly reduced myocardial infarct size and improved LV contractility at a dose (3 mg/kg) with systemic vasodilating effects but not at a lower dose (0.3 mg/kg) without hemodynamic effects.     

奥美沙坦酯治疗轻度及中度原发性高血压疗效和安全性的评价

目的:评价奥美沙坦酯治疗轻度及中度原发性高血压的疗效和安全性。方法:80例轻度及中度原发性高血压患者随机接受奥美沙坦酯20 mg或缬沙坦80 mg治疗,每日1次,总疗程8周。结果:奥美沙坦酯组治疗前的收缩压(SBP)/舒张压(DBP)为(155.2±11.4)/(96.1±5.2)mmHg(1 mmHg=0.133 kPa),治疗后的血压为(138.8±10.2)/(86.5±4.8)mmHg,血压下降幅度为(16.4±8.1/9.6±5.1)mmHg。缬沙坦组治疗前的SBP/DBP为(156.1±12.2)/(97.2±5.1)mmHg,治疗后的血压为(139.5±10.4)/(88.0±5.5)mmHg,血压下降幅度为(15.6±7.8/9.1±4.9)mmHg。2组治疗前后血压下降幅度差异均有统计学意义(P<0.01),2组间差异无统计学意义(P>0.05)。奥美沙坦酯组和缬沙坦组降压显效率分别为59.0%和60.5%,总有效率分别为87.2%和86.8%,2组间差异无统计学意义。本实验中奥美沙坦酯组出现不良反应者少。结论:奥美沙坦酯治疗轻度及中度原发性高血压疗效确切,且安全可靠。     

伊贝沙坦对缺血再灌注心律失常的作用实验研究

目的:探讨血管紧张素Ⅱ受体拮抗剂伊贝沙坦对缺血再灌注心律失常的作用及其机制。方法:32只Sprague-Dawley雄性大鼠分为缺血/复灌对照组,缺血/复灌+伊贝沙坦(100umol/L)组,缺血/复灌+伊贝沙坦(50umol/L)组,缺血/复灌+伊贝沙坦(100umol/L)+CsA(1umol/L)组,每组8只。观察各组心脏离体灌注下左室发展压(LVDP)、左室舒张末压(LVEDP)、心率(HR)、最大收缩/舒张速率(±dP/dtmax)、冠脉流量(CF)、灌流液乳酸脱氢酶(LDH)及心律失常评分。结果:单用伊贝沙坦组LVDP、LVEDP、LDH及心律失常评分显著低于缺血/复灌对照组(P<0.01);±dP/dtmax、CF显著高于缺血/复灌对照组(P<0.05),合灌环胞菌素A可以部分甚至全部逆转伊贝沙坦的作用。结论:伊贝沙坦对离体大鼠缺血/再灌注心肌有保护作用,减少再灌注心律失常发生,部分可能是通过激活钙调神经磷酸酶起作用。     

Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension

BACKGROUND/AIMS: To assess the effects of the early and chronic administration of losartan--a specific angiotensin II receptor antagonist--in the prevention of hepatic fibrosis and portal hypertension. METHODS/RESULTS: (1) In CCl(4) rats, losartan at 5 and 10 mg/kg per day significantly decreased portal pressure (-11, -18%, respectively), splenorenal shunt blood flow (-60, -80%) and liver fibrosis (liver hydroxyproline and area of fibrosis) without significant changes in mortality and mean arterial pressure (MAP). (2) In bile duct ligated (BDL) rats, losartan at 5 mg/kg per day significantly decreased portal pressure (-14%), splenorenal shunt blood flow (-70%) and liver fibrosis. Losartan at 10 mg/kg per day significantly worsened liver and renal functions, mortality and liver fibrosis, without significant changes in portal pressure and splenorenal shunt blood flow. Losartan at 5 and 10 mg/kg per day significantly decreased MAP (-24, -30%). (3) In portal vein ligated (PVL) rats, losartan significantly decreased MAP (-12%) but did not change portal pressure or splenorenal shunt blood flow. CONCLUSIONS: In BDL and CCl(4) rats, losartan has beneficial effects on splanchnic hemodynamics and liver fibrosis. Losartan might decrease hepatic resistances in fibrotic liver. Losartan decreased MAP except in CCl(4) rats. Higher dosage of losartan had deleterious effects in BDL rats.     

ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells

AIM: To investigate the effects of nicotine and nicotine plus angiotensin II receptor blocker (ARB) on the gene expression profile of human coronary artery endothelial cells (HCAECs). METHODS: The changes in gene expression profiles in HCAECs treated with nicotine and nicotine plus ARB olmesartan were analyzed by DNA microarray. In nicotine-treated HCAECs, 432 genes selected by P < 0.01 were greater than 1.5-fold compared with the untreated cells. Data were analyzed using IPA (Ingenuity^® Systems, www.ingenuity.com). RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to “cardiovascular function and disease”, were significantly increased. In canonical pathway analyses using IPA, “atherosclerosis signaling” was strongly affected by nicotine treatment and this effect was reduced by co-incubation with ARB olmesartan. These data indicate that the deleterious cardiovascular consequences of cigarette smoking may, at least in part, be due to the nicotine-induced gene expression profile related to “atherosclerosis signaling”. CONCLUSION: The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects that are independent of those from lowering the blood pressure.     

奥美沙坦对心力衰竭大鼠肺脏肾上腺素能受体表达的影响

目的:研究奥美沙坦对心力衰竭大鼠肺脏α1A-肾上腺素受体(α1A-AR)和β1、β2肾上腺素受体(β-AR)表达水平及对血浆肾素活性(plasma rennin activity,PRA)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平的影响。方法:45只Wistar大鼠随机分为正常对照组(A组)、假手术组(B组)、心力衰竭模型对照组(C组)和奥美沙坦组(D组),采用灌胃法给药。超声心动图检测用药前后大鼠心脏功能,灌胃治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。超声心动图检测用药前后大鼠心脏功能。治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。结果 :用药前A组与B组比较,大鼠左心室射血分数(LVEF)组间差异无统计学意义(P>0.05);与B组比较,C组、D组大鼠LVEF明显降低(均P<0.05)。用药后,与C组比较,D组LVEF显著改善(P<0.05)。用药后,A组与B组大鼠PRA、AngⅡ水平差异无统计学意义(P>0.05);与B组比较,C组大鼠PRA、AngⅡ水平明显升高(P<0.01);与C组比较,D组大鼠血浆PRA、AngⅡ水平明显降低(P<0.05);在蛋白质表达水平,A组与B组用药后比较,各受体水平差异无统计学意义(P>0.05)。与B组比较,C组大鼠α1A-AR、β1-AR表达水平显著下调(P<0.05),β2-AR表达水平明显上调(P<0.01);与C组相比,D组α1A-AR、β1-AR及β2-AR水平均显著升高(均P<0.05)。结论:奥美沙坦能够改善心肌梗死后心力衰竭大鼠的心脏功能,提高LVEF,同时能够降低心力衰竭时血浆中升高的PRA和AngⅡ,并使心力衰竭大鼠肺脏下调的α1A-AR、β1-AR上调,表达增加的β2-AR进一步上调。奥美沙坦对慢性心力衰竭(chronic heart failure,CHF)时交感-肾上腺素系统激活后肾上腺素受体表达的调节作用和对PRA、AngⅡ的抑制作用,有利于维持心力衰竭时肺脏的通气/血流比值,减轻肺水肿,改善心力衰竭时的肺循环淤血,对CHF的肺脏起到了有益的保护作用。     

Angiotensin II Type 1 Receptor Antagonist Suppress Angiogenesis and Growth of Gastric Cancer Xenografts

Angiotensin II (Ang II) has been reported to promote tumor progression, tumor growth and angiogenesis in many cancers. We previously observed that angiotensin II type1 receptors (AT1R) were upregulated in human gastric cancer and may be involved in the progression of gastric cancer. We studied the effects of AT1R antagonist on angiogenesis and growth in gastric cancer xenografts to observe the mechanism action of AT1R in the gastric cancer. The results showed that the growth of gastric cancer cells was significantly suppressed by treatment with AT1R antagonist. In vivo, TCV-116, at doses of both 2 and 5 mg/kg/day, significantly suppressed tumor growth in mice (47.3 and 70.2%). Microvessel density was significantly decreased by TCV-116 (3.4 ± 0.9 and 2.8 ± 0.5 per field) compared with the control group (12.9 ± 1.1 per field), and VEGF expression was significantly suppressed by AT1R antagonist. These results demonstrate that AT1R plays an important role in the progression of gastric cancer. Suppression tumor angiogenesis could be one of the mechanisms by which AT1R antagonist suppresses the growth of gastric cancer. These findings also provide a theoretical basis for the future clinical application of AT1R antagonist against gastric cancer.     

奥美沙坦酯与左旋氨氯地平合用对高血压蛋白尿的作用

目的观察奥美沙坦酯与左旋氨氯地平联合应用对高血压患者蛋白尿的临床疗效。方法将90例高血压合并肾脏损害蛋白尿的患者随机分为A、B两组。A组给予奥美沙坦酯20mg／d和左旋氨氯地平2．5mg／d,B组给予左旋氨氯地平2．5mg／d和氢氯噻嗪12．5mg／d,控制血压及消退蛋白尿,均治疗6个月。观察两组治疗前后血压、24h尿白蛋白总量的变化。结果治疗6个月后,A、B两组血压明显下降（P〈0．01）,A组下降[（28．1±1．9）／（32．6±3．9）mmHg]与B组下降[（27．8±3．1）／（31．8±1．7）mmHg]比较差异无统计学意义（P〉0．05）。A、B两组尿蛋白均下降,但A组下降[（0．79±0．09）g／24h]较B组[（0．41±0．13）g／24h]下降更明显,差异有统计学意义（P〈0．01）。结论奥美沙坦酯与左旋氨氯地平合用能较平稳降低血压,显著减少尿蛋白,有效保护肾脏。     

Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI

Background Although angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios (HR): 2.124, 95% confidence interval (95% CI): 1.048–4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group (P = 0.04). In regard to the secondary endpoints, there were no significant differences between the two treatment arms (P = 0.137, HR: 1.454,95% CI: 0.888–2.380). Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.     

AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice

Although it has been suggested that the renin–angiotensin (RA) system and cathepsins contribute to the development and vulnerability of atherosclerotic plaque, the interaction of the RA system and cathepsins is unclear. Thus, we investigated the effects of an angiotensin II type 1 receptor (AT1) antagonist, olmesartan, on the levels of cathepsins in brachiocephalic atherosclerotic plaque and plaque stabilization in apolipoprotein E (apoE)-deficient mice receiving a high-fat diet.Under a high fat diet, treatment with olmesartan (3 mg/kg per day) maintained collagen and elastin at high levels and attenuated the plaque development and cathepsin S (Cat S) level in the atherosclerotic plaque of apoE-deficient mice. The administration of olmesartan suppressed the accumulation of macrophages in plaque. Immunoreactivities of Cat S and AT1 were observed in macrophages. The amount of Cat S mRNA and the macrophage-mediated collagenolytic and elastolytic activities in cultured macrophages were increased by exposure to angiotensin II (Ang II), and these effects were diminished by olmesartan and the NADPH-oxidase inhibitor apocynin. These results suggested that Cat S derived from macrophages is involved in the mechanisms of atherosclerotic plaque vulnerability, and AT1 blocker maintained the plaque stabilization alongside the suppression of Cat S and macrophage activities.     

Olmesartan, a novel angiotensin II type 1 receptor antagonist, reduces severity of atherosclerosis in apolipoprotein E deficient mice associated with reducing superoxide production

Background and aim

Oxidative stress may play an important role in the development of atherosclerosis. Some angiotensin II type 1 (AT₁) receptor antagonists have the capacity of reducing oxidative stress in addition to the hemodynamic actions. Accordingly, we assessed the hypothesis that olmesartan, a novel AT₁ receptor antagonist, reduced the severity of atherosclerosis in apolipoprotein (apo) E-deficient mice associated with reducing oxidative stress.

Methods and results

Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Mice were intraperitoneally treated with an injection of olmesartan (1 mg/kg/day) daily over 8 weeks, and were compared with the untreated controls. Blood pressure was not changed significantly by the olmesartan treatment. Fatty streak plaque developed in apo E-deficient mice, and was suppressed in mice that received olmesartan. In addition, olmesartan reduced not only superoxide production but the overload of oxidative stress in aortic walls. There were no significant differences in serum lipid levels between olmesartan-treated and -untreated groups. In vitro study showed that both olmesartan and its active metabolite RNH-6270, an enantiomer of olmesartan, suppressed interferon-γ, macrophage inflammatory protein-2, and thioredoxin (a marker of oxidative stress) concentrations in cultured cells.

Conclusion

Olmesartan may suppress atherosclerosis via reducing not only superoxide production but also the overload of oxidative stress in this animal model.