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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of type-2 diabetes is increasing throughout the world. By 2010, 350 million people will have this disease. Microalbuminuria is present in more than one third, for some at diabetes diagnosis. Rather than a complication, it is an indication of a vascular disorder that is part of the metabolic syndrome. 25% will develop end-stage kidney failure. Several studies have identified microalbuminuria or proteinuria as an independent cardiovascular risk factor. Others have shown that antihypertensive treatments acting on the renin-angiotensin system (ACE inhibitors, ARBs agents) can reduce the progression of nephropathy in people with hypertension, type 2 diabetes and microalbuminuria. The "nephroprotective" effects of these drug classes, beyond their role in blood-pressure reduction, are suggested by modifications in renal structure and protein expression. But no study has so far examined their value in primary prevention in persons with type 2 diabetes without--but at risk of developing--microalbuminuria. The Roadmap study (Randomized Olmesartan And Diabetes Microalbuminuria Prevention Study) of primary prevention has as its objective measurement of the impact of ARBs (olmesartan 40 mg/d) treatment on renal outcome in 4400 patients with type 2 diabetes without microalbuminuria. Follow-up of this placebo-controlled study will last for 5 years. Conducted in 200 European centers, its results are expected for 2012.
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PMID:[Primary cardiorenal prevention in patients with type-2 diabetes. The Roadmap study]. 1626 93

Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed. Olmesartan and a non-specific vasodilator hydralazine lowered systolic blood pressure of mice on day 7 after virus inoculation to a similar extent. Olmesartan significantly decreased myocardial inflammation compared with controls, whereas hydralazine significantly increased this. Olmesartan significantly decreased the expression of IFN-gamma (interferon-gamma), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating that olmesartan suppressed the activation of infiltrating killer lymphocytes. Olmesartan also decreased the expression of CVB3 genomes in myocardial tissue as well as serum levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine), a biomarker of oxidative-stress-induced DNA damage. The findings suggest that olmesartan prevents myocardial damage and may improve the prognosis of patients with acute myocarditis; however, further investigations are needed before clinical use.
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PMID:Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3. 1633 7

HIV-associated nephropathy (HIVAN) is characterized by a collapsed glomerular capillary tuft with hyperplasia and hypertrophy of podocytes. Recently generated were conditional transgenic mice (podocin/Vpr) that express one of the HIV-1 accessory genes, vpr, selectively in podocytes using podocin promoter and Tet-on system. These transgenic mice developed renal injury similar to HIVAN when treated with doxycycline for 8 to 12 wk. This study demonstrated that nephron reduction by heminephrectomy markedly enhanced phenotypic changes of podocytes and led to severe FSGS within 4 wk. Nephrotic-range proteinuria was observed already at 2 wk, together with dedifferentiation and dysregulation of podocytes, indicated by decreased expression of nephrin, synaptopodin, and Wilms' tumor 1 protein and increased expression of Ki-67. The acceleration of phenotypic changes of podocytes, proteinuria, and subsequent glomerulosclerosis by heminephrectomy was almost completely inhibited by angiotensin II type 1 receptor (AT1R) blocker olmesartan. In contrast, the renoprotective effect of the calcium channel antagonist azelnidipine was minimal, although it lowered systemic BP to the same level as olmesartan, demonstrating that the inhibitory effect of AT1R blocker was independent of systemic BP. Olmesartan also reduced proteinuria and prevented glomerulosclerosis even by the delayed treatment, which was initiated after the podocyte injury appeared. These data suggest that nephron reduction exaggerates podocyte injury and subsequent glomerulosclerosis, possibly through glomerular hypertension, in the mouse model of HIVAN. AT1R blockade could be beneficial in the treatment of HIVAN by ameliorating podocyte injury by avoiding the vicious cycle of nephron reduction and glomerular hypertension.
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PMID:Angiotensin II type 1 receptor blockade inhibits the development and progression of HIV-associated nephropathy in a mouse model. 1722 13

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.
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PMID:Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. 1734 82

The therapeutic control of hypertension is still a global challenge and frequently requires combination therapy. Olmesartan medoxomil hydrochlorothiazide (Olmetec plus, Belsar plus) is a fixed-dose combination of olmesartan 20 mg and hydrochlorothiazide 12.5 or 25 mg. Olmesartan is a well known angiotensin II AT1 receptor blocker characterized by a good efficacy, a fast and prolonged duration of action and a placebo-like tolerability. With the combination therapy, no significant change of pharmacokinetics of either component is observed. The fixed-dose combination results in a greater blood pressure reduction compared to monotherapy with either component. This is at least effective as or even more effective than the combination of atenolol or losartan with hydrochlorothiazide, respectively. The responder rate is about 90%. The safety and tolerability remain excellent. Beyond the antihypertensive effect, olmesartan significantly reduces vascular inflammation and the wall-to-lumen ration in arteries. The starting dose is 20/12.5 mg.
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PMID:[Medication of the month. Olmesartan medoxomil hydroclorothiazide (Olmetec Plus or Belsar Plus]. 1751 87

Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that has been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. It is a prodrug that is hydrolysed in the gut into its active metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II type 1 receptor (AT1) to which it binds completely and insurmountably and has very little affinity for the other receptor subtypes AT2 and AT4. After oral administration, in animals and humans, it achieves a maximal blood drug concentration within a maximal time of approximately 2 h. It is then slowly eliminated in the urine and faeces. His half-life is approximately 13 h, which makes it suitable for once-daily administration. Olmesartan medoxomil given orally in single daily doses of 20-40 mg has demonstrated significant blood pressure (BP) lowering effects in hypertensive patients. A medline search for the preparation of this manuscript was conducted and revealed 128 references, from 2000 to 2007. Of these, only 16 well-designed prospective clinical trials were selected. The remaining were either animal studies, reviews or studies in progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated similar antihypertensive actions to the other antihypertensive drugs, as well as other members of its class given the highest recommended doses. In addition, the BP lowering effect of olmesartan, like the other members of its class, is greatly enhanced in combination with a diuretic. Its safety profile is similar to the other ARBs and no different than placebo.
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PMID:Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update. 1755 45

Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan.
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PMID:Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension. 1836 12

In addition to the juxtaglomerular apparatus, renin is also synthesized in renal tubular epithelium, including the collecting duct (CD). Angiotensin (Ang) II differentially regulates the synthesis of juxtaglomerular (inhibition) and CD (stimulation) renin. Because diabetes mellitus, a disease with high intrarenal renin-Ang system and Ang II activity, is characterized by high prorenin levels, we hypothesized that the CD is the major source of prorenin in diabetes. Renin granular content was visualized using in vivo multiphoton microscopy of the kidney in diabetic Munich-Wistar rats. Diabetes caused a 3.5-fold increase in CD renin, in contrast to less pronounced juxtaglomerular changes. Ang II type 1 receptor blockade with Olmesartan reduced CD renin to control levels but significantly increased juxtaglomerular renin. Using a fluorogenic renin assay, the prorenin component of CD renin content was measured by assessing the difference in enzymatic activity of medullary homogenates before and after trypsin activation of prorenin. Trypsinization caused no change in control renin activity but a 5-fold increase in diabetes. Studies on a CD cell line (M1) showed a 22-fold increase in renin activity after trypsinization and a further 35-fold increase with Ang II treatment. Therefore, prorenin significantly contributes to baseline CD renin. Diabetes, possibly via Ang II, greatly stimulates CD prorenin and causes hyperplasia of renin-producing connecting segments. These novel findings suggest that, in a rat model of diabetes, prorenin content and release from the CD may be more important than the juxtaglomerular apparatus in contrast to the existing paradigm.
Hypertension 2008 Jun
PMID:The collecting duct is the major source of prorenin in diabetes. 1841 93

Dietary obesity is associated with type 2 diabetes and cardiovascular diseases, although the underlying mechanism is unknown. This study was undertaken to elucidate the role of angiotensin II and apoptosis signal regulating kinase-1 (ASK1) in obesity/diabetes-associated cardiovascular complications and hepatic steatosis. Mice fed a high-fat diet were treated with olmesartan, an angiotensin II type 1 receptor blocker, to elucidate the role of angiotensin II in diabetic mice. Treatment of mice fed a high-fat diet with olmesartan markedly suppressed cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling, induced by obesity/diabetes. Moreover, olmesartan suppressed the disruption of the vascular endothelial NO synthase dimer in diabetic mice. Olmesartan also significantly prevented hepatic steatosis and fibrosis in diabetic mice. These beneficial effects of olmesartan on diabetic mice were associated with the attenuation of ASK1 activation in these mice. ASK1-deficient mice and wild-type mice were compared, regarding the effects of a high-fat diet. A comparison between ASK1-deficient and wild-type mice showed that ASK1 deficiency attenuated cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling induced by obesity/diabetes. The amelioration of vascular endothelial impairment by ASK1 deficiency was attributed to the prevention of endothelial NO synthase dimer disruption. ASK1 deficiency also significantly lessened hepatic steatosis in diabetic mice. In conclusion, our work provided the evidence that ASK1 is significantly activated in diet-induced diabetic mice and contributes to cardiovascular diseases and hepatic steatosis in diabetic mice. Moreover, the beneficial effects of angiotensin II inhibition on dietary diabetic mice seem to be mediated by the inhibition of ASK1 activation.
Hypertension 2008 Sep
PMID:Olmesartan prevents cardiovascular injury and hepatic steatosis in obesity and diabetes, accompanied by apoptosis signal regulating kinase-1 inhibition. 1867 90

Elevated systolic blood pressure increases the risk of cardiovascular events, as shown by a number of meta-analyses of large-scale clinical trials. As concerns the prognostic impact of the metabolic syndrome on cardiovascular events, few large-scale studies are available in the Japanese hypertensive population. The prospective, large-scale, observational OMEGA (Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement) study sought to examine the relationship between the incidence of cardiovascular disease (CVD) and achieved blood pressure, metabolic syndrome, lifestyle factors and other risk factors for CVD in patients with hypertension. Of the 15,313 enrolled patients from 2,219 institutions in Japan, we report here the baseline characteristics of the 14,841 eligible patients whose baseline data were collected as of October 31, 2007. Men and women 50 to 79 years old (mean age 65) with physician-diagnosed hypertension were enrolled, and all patients were treated with open-label olmesartan medoxomil (5 to 40 mg daily). The majority of patients (75%) had mild to moderate hypertension. The prevalences of dyslipidemia and diabetes mellitus were 48% and 24%, respectively. The metabolic syndrome was identified in 48% and 19% of the evaluable men and women, respectively, using the criteria of the Japanese Society of Internal Medicine. Men with the metabolic syndrome were at the greatest risk for CVD, and a greater proportion of men than of women had all five metabolic syndrome components. The complete follow-up data from the OMEGA study will provide much-needed information to guide treatment in patients with hypertension and the metabolic syndrome. (Hypertens Res 2008; 31: 2011-2017).
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PMID:OMEGA study: design, baseline data, metabolic syndrome prevalence in a large-scale observational study of hypertensive patients: The Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement study. 1909 72


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