Disease relevance of Olmetec

• Olmesartan also reduced proteinuria and prevented glomerulosclerosis even by the delayed treatment, which was initiated after the podocyte injury appeared [1].
• Cortical tissue hypoxia in the early phase (4 and 7 d) in remnant kidney rats, sham-operated rats, and animals treated with the angiotensin II receptor blocker (ARB) olmesartan (10 mg/kg per d) was assessed by uptake of a hypoxic probe, pimonidazole, expression of HIF-1alpha, and by increased transcription of hypoxia-responsive genes [2].
• The role of olmesartan medoxomil in the management of hypertension [3].
• After 6 months of treatment with olmesartan, intimal hyperplasia was significantly lower than before treatment [4].
• Moreover, azelnidipine synergistically enhanced the inhibitory action of olmesartan on brain ischemia, suggesting beneficial combined effects of a CCB with an AT1 receptor blocker on ischemic brain damage [5].

High impact information on Olmetec

• Olmesartan also suppressed lymphocyte proliferation in mice immunized with ovalbumin in alum [6].
• 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 [1].
• In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment [7].
• Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment [7].
• Six groups of 50 gerbils were treated either with placebo, erythropoietin (intraperitoneally, 5000 IU/kg, 2 and 48 h after stroke), olmesartan (10 mg/kg per day in drinking water started 36 h after stroke), ramipril (2.5 mg/kg per day in drinking water started 36 h after stroke), erythropoietin + olmesartan, or erythropoietin + ramipril [8].

Chemical compound and disease context of Olmetec

• Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension [9].
• At dosages of 5 to 20 mg/day, olmesartan medoxomil was more effective than captopril 12.5 to 50mg twice daily at lowering seated DBP in patients with mild to moderate hypertension in a dose titration study [10].
• The AII infusion led to significant elevations in TC and non-HDL-C in the fructose-fed rats, and olmesartan treatment completely rectified this AII-induced hypercholesterolemia [11].
• An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells [12].
• Dual therapy with pravastatin and olmesartan, which produced an additive reduction in cardiomyocyte hypertrophy and cardiac fibrosis after myocardial infarction through different mechanisms, decreases the propensity of the heart to arrhythmogenesis [13].

Biological context of Olmetec

• Olmesartan restored the blood pressure to normal as expected, but it exerted no effect in suppressing AII-induced hyper-TG or -FFA [14].
• Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients [15].
• Temocapril and CS-866 lowered systolic blood pressure, improved insulin resistance, and reduced TNF-alpha in both skeletal muscles [16].
• Moreover, olmesartan enhanced the insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 induced in skeletal muscle, whereas azelnidipine did not change it [17].
• However, compared with either drug alone, combined olmesartan and pravastatin prevent cardiomyocyte hypertrophy to a larger extent, which was further confirmed by downregulation of the left ventricular atrial natriuretic peptide mRNA [13].

Anatomical context of Olmetec

• Acetylcholine-induced relaxation in isolated carotid arteries was significantly less in the high-cholesterol diet placebo-treated group compared to the normal diet group, whereas its response was improved by olmesartan [4].
• In analysis by flow cytometry of binding experiments performed in brush-border membrane vesicles isolated from kidneys of CD-1 mice, anti-megalin antisera interfered with ANG-(1-7) binding more strongly than olmesartan (P < 0.05 against positive control) [18].
• Both temocapril and olmesartan significantly improved the M value and decreased blood pressure and adipocyte size without change in %fat pads in FFR [19].
• The c-Jun NH(2)-terminal kinase (JNK) activity was elevated in the left ventricle of obese mice (western) and blocked by temocapril and olmesartan [20].
• Immunostaining intensities in rats treated with olmesartan (n = 5) were also associated with increased (P < 0.05) ACE2 and angiotensin-(1-7) in thoracic aorta media compared with vehicle-treated rats [21].

Associations of Olmetec with other chemical compounds

• BACKGROUND: Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype [15].
• Twenty-four hour ambulatory blood pressure measurements, plasma renin activity (PRA), Ang II and concentrations of RNH-6270, the pharmacologically active metabolite of CS-866, were monitored up to 24 h after medication [22].
• Moreover, the co-administration of lower doses of azelnidipine (0.1 mg/kg a day) and olmesartan (1 mg/kg a day) significantly inhibited the atherosclerotic area and oxidative stress, whereas azelnidipine or olmesartan alone at these doses did not affect these parameters [23].
• RESULTS: Olmesartan did not significantly affect blood pressure or plasma cholesterol levels throughout the experiment [4].
• In well designed randomised trials, olmesartan medoxomil was significantly more effective than placebo, and at dosages of 10 to 20 mg/day was at least as effective as atenolol 50 to 100 mg/day in reducing diastolic blood pressure (DBP) [10].

Gene context of Olmetec

• Olmesartan inhibited the hypoxia-induced phosphorylation of ERK1/2 in the lung, but not in the right ventricle [24].
• Angiotensin II receptor blockade with CS-866 (1 mg kg-1 day-1) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure [25].
• ATP-dependent uptake of olmesartan was observed in both human canalicular membrane vesicles (hCMVs) and MRP2-expressing vesicles [26].
• Ang II significantly up-regulated VEGF mRNA levels in MOLT-3 T cells, which was inhibited by PEDF or olmesartan, an Ang II type 1 receptor blocker [27].
• Male Sprague-Dawley rats (200 to 220 g) were divided into 3 groups: sham surgery (n=10), subcutaneous infusion of Ang II (80 ng/min, n=11), and Ang II infusion plus AT1 blocker (ARB), olmesartan (5 mg/d, n=12) [28].

Analytical, diagnostic and therapeutic context of Olmetec

• The control group was fed a normal diet.RESULTS Blood pressure and the plasma cholesterol level were not affected by CS-866 [29].
• DESIGN: Following a four-way crossover protocol, two groups of eight patients with mild-to-moderate hypertension received a sodium-restricted diet (60 mmol daily) and ingested single doses of 2.5, 10 and 40 mg or 5, 20 and 80 mg of CS-866, respectively, or placebo [22].
• MATERIALS AND METHODS: In this study we compared the effects of CS-866, a new angiotensin II type 1 receptor antagonist, to that of an ACE inhibitor, temocapril hydrochloride, on the development and progression of diabetic nephropathy using Otsuka Long-Evans Tokushima fatty rats, a type II diabetes mellitus model animal [30].
• Numbers of myocardial interleukin-1beta (IL-1beta)-positive-staining cells (obtained by immunohistochemistry) and quantities of IL-1beta expression (obtained by Western blotting) were significantly lower in rats with EAM given olmesartan treatment compared with rats given vehicle [31].
• 2. Olmesartan (1 mg kg(-1) per day) was orally administered to fibrotic rats, induced by bile duct ligation [12].

References