"Temocapril"

whether gene expressions are modulated by ACEI (temocapril), ARB (olmesartan) or both in a murine model with transverse aortic constriction (TAC) and confirm whether periostin is a target gene of olmesartan in mice with myocardial infarction (MI). We detected 109 genes that were significantly up-regulated in TAC mice and a majority of these were down-regulated in response to temocapril, olmesartan or their combination which significantly attenuated cardiac remodeling at one or four weeks. Real-time RT-PCR demonstrated that olmesartan, temocapril or their combination down-regulated the expression of periostin. In MI mice treated with olmesartan for 4 weeks, the left ventricular end-diastolic and systolic dimensions measured with echocardiography were lower, whereas maximum rate of rise and fall rate of LV

InhibitorsNames: Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Quinapril, Benazepril, Cilazapril, Fosinopril, Trandolapril, Spirapril, Delapril, Moexipril, Temocapril, Zofenopril, ImidaprilMedications: Angiotensin II receptor BlockersNames:Losartan, Eprosartan, Valsartan, Irbesartan, Tasosartan, Candesartan, Telmisartan, Olmesartan medomoxil, Azilsartan medomoxil, FimasartanMedication: DRIName

Angiotensin-Converting Enzyme Inhibitor Does Not Suppress Renal Angiotensin II Levels in Angiotensin I–Infused Rats Angiotensin II (Ang II) infusion into rats elevates local angiotensin II levels through an AT1 receptor-dependent pathway in the kidney. We examined whether treatment with an angiotensin-converting enzyme (ACE) inhibitor, temocapril, or an AT1-receptor blocker, olmesartan , prevented elevation of Ang II levels in the kidney of angiotensin I (Ang I)-infused rats. Rats were infused with Ang I (100 ng/min) and treated with temocapril (30 mg/kg per day, n = 10) or olmesartan (10 mg/kg per day, n = 9) for 4 weeks. Ang I infusion significantly elevated blood pressure compared with vehicle-infused rats (n = 6). Treatment with temocapril or olmesartan suppressed Ang I-induced

(temocapril), an ECE/NEP inhibitor (CGS 26303), or a NEP inhibitor (CGS 24592) from the LVH stage (11 weeks) to the CHF stage (17 weeks). All treatments decreased the systolic blood pressure equally and significantly improved LV fractional shortening. Both temocapril and CGS 26303 ameliorated LV perivascular fibrosis, reduced mRNA levels of types I and III collagen, and decreased the heart weight/body weight ratio. CHF rats had increased plasma ET-1 levels compared with control rats. Only CGS 26303 reduced ET-1 to normal levels. ET-1 levels were found to correlate with heart/body weight, right ventricle/body weight and perivascular fibrosis ratios. During the transition to CHF, CGS 26303 produces effects that are comparable to temocapril and superior to CGS 24592. The beneficial effects of CGS 26303

by chromatin staining of en face specimens with Hoechst 33342. Although activity of angiotensin-converting enzyme in arterial homogenates was not increased, administration of an angiotensin-converting enzyme inhibitor temocapril for 3 days before H2O2 treatment inhibited EC apoptosis, followed by reduced neointimal formation 2 weeks later. Also, an angiotensin II type 1 (AT1) receptor blocker (olmesartan , temocapril and olmesartan reduced apoptosis and 8-isoprostane formation induced by H2O2, suggesting that endogenous angiotensin II interacts with H2O2 to elevate oxidative stress levels and EC apoptosis. Neither an AT2 receptor blocker, PD123319, affected H2O2-induced apoptosis, nor a NO synthase inhibitor, NG-nitro-L-arginine methyl ester, influenced the effect of temocapril on apoptosis in cell culture

in ovariectomized mice, whereas co-administration of olmesartan and 17beta-estradiol at these doses attenuated these parameters. An angiotensin-converting enzyme (ACE) inhibitor, temocapril, also inhibited atherosclerotic changes similarly to olmesartan. Moreover, angiotensin II-mediated activation of NAD(P)H oxidase in cultured vascular smooth muscle cells was attenuated by 17beta-estradiol. These results

) at advanced stage of DHF in hypertensive rats. Dahl salt-sensitive rats fed 8% NaCl diet from age 7 weeks served as DHF model, and those fed a normal chow served as control. The DHF model rats were arbitrarily assigned to 3 treatment regimens at age 17 weeks: ACEI (temocapril 0.4 mg/kg per day), combination of ACEI (temocapril 0.2 mg/kg per day) with ARB (olmesartan 0.3 mg/kg per day), or placebo. At age 17

pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure

transporter 4 (GLUT4), resulting in improvement of insulin resistance. Administration of an ACE inhibitor, temocapril, significantly decreased plasma glucose and insulin concentrations in type 2 diabetic mouse KK-Ay. Mice treated with temocapril showed a smaller plasma glucose increase after glucose load. We demonstrated that temocapril treatment significantly enhanced 2-[3H]-deoxy-D-glucose (2-DG) uptake in skeletal muscle but not in white adipose tissue. Administration of a bradykinin B2 receptor antagonist, Hoe140, or an NO synthase inhibitor, L-NAME, attenuated the enhanced glucose uptake by temocapril. Moreover, we observed that translocation of GLUT4 to the plasma membrane was significantly enhanced by temocapril treatment without influencing insulin receptor substrate-1 phosphorylation. In L6 skeletal

-sensitive rats fed a diet containing 8% NaCl from age 7 weeks (DHF model) were divided into three groups: six untreated rats, six rats treated with a subdepressor dose of an ARB, candesartan cilexetil (1 mg/kg per day), from age 8 weeks, and six rats treated with a subdepress or dose of an ACEI, temocapril hydrochloride (0.2 mg/kg per day), from age 8 weeks. Six Dahl salt-sensitive rats fed on normal chow

with a vehicle or with 1 mg/kg per day of temocapril, an angiotensin-converting enzyme inhibitor, or 0.1 mg/kg per day of olmesartan, an angiotensin II type 1 receptor blocker, for the last 2 weeks. Insulin sensitivity (M value: mg/kg per min) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Sizes of adipocytes derived from epididymal fat and triglyceride content in the soleus muscle were determined. FFR had lower M value, higher blood pressure, larger adipocyte size, higher ratio of epididymal fat pads over body weight (%fat pads), and higher intramuscular triglyceride than did the control rats. Both temocapril and olmesartan significantly improved the M value and decreased blood pressure and adipocyte size without change in %fat pads in FFR. Adipocyte size was negatively correlated

of ADMA were not prevented by supplementation of l-arginine, and vascular NO production was not reduced by ADMA treatment. Treatment with ADMA caused upregulation of angiotensin-converting enzyme (ACE) and an increase in superoxide production that were comparable in both strains and that were abolished by simultaneous treatment with temocapril (ACE inhibitor) or olmesartan (AT(1) receptor antagonist

synthase (eNOS) is an important source. Angiotensin-converting enzyme (ACE) inhibitors are known to enhance EDHF-mediated responses. In this study, we examined whether endothelium-derived H2O2 accounts for the enhancing effect of an ACE inhibitor on EDHF-mediated responses and, if so, what mechanism is involved. Control and eNOS-/- mice were maintained with or without temocapril (10 mg/kg per day orally ) for 4 weeks, and isometric tensions and membrane potentials of mesenteric arteries were recorded. In control mice, temocapril treatment significantly enhanced EDHF-mediated relaxations and hyperpolarizations to acetylcholine (n=8 each). Catalase, a specific scavenger of H2O2, abolished the beneficial effects of temocapril, although it did not affect endothelium-independent relaxations to sodium

) Wistar-Kyoto rats were treated with vehicle, temocapril, CS-866 (an angiotensin II type 1 receptor antagonist), cerivastatin, or hydralazine for 2 weeks. Endothelium-dependent relaxations (EDRs) of aortas from aged rats were markedly impaired compared with EDRs of aortas from young (3-month-old) rats. Indomethacin, NS-398 (a cyclooxygenase [COX]-2 inhibitor), and SQ-29548 (a thromboxane A2 /prostaglandin H2 receptor antagonist) acutely restored EDRs in aged rats, suggesting an involvement of COX-2-derived vasoconstricting eicosanoids. Tiron, a superoxide scavenger, also partially improved EDRs, suggesting an involvement of superoxide. EDRs were significantly ameliorated in aged rats after long-term treatment with temocapril or CS-866 but not after treatment with cerivastatin or hydralazine

effective on cardiac remodeling than each agent alone. In this study, we compared the effects of an ACE inhibitor (temocapril), an ARB (CS-866), and their combination on cardiac remodeling after MI. Temocapril at 3 or 30 mg/kg/day, CS-866 at 1 or 10 mg/kg/day, or combined temocapril and CS-866 at 1.5 and 0.5 mg/kg/day or at 15 and 5 mg/kg/day, respectively, were administered to rats after MI. At 4 weeks

Temocapril prevents transition to diastolic heart failure in rats even if initiated after appearance of LV hypertrophy and diastolic dysfunction. Congestive heart failure with left ventricular (LV) diastolic dysfunction and preserved systolic function, i.e. diastolic heart failure (DHF), is often observed in hypertensive patients. Although angiotensin converting enzyme (ACE) inhibitors are widely used as antihypertensive therapy, there is a continued controversy about long-term effect of ACE inhibition on diastolic function. The current study was designed to elucidate a therapeutic effect of ACE inhibitor, temocapril, administration initiated after LV hypertrophy (LVH) and diastolic dysfunction are evident. Dahl salt sensitive rats fed on 8% NaCl diet from 7 weeks (hypertensive DHF model

with that of adding ARB following a relatively low dose of ACE-I on the survival and left ventricular (LV) remodeling after MI. Rats underwent left coronary artery ligation and were treated with either ACE-I temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after the surgery. The rats treated with temocapril were further randomly assigned to receive either high-dose temocapril (10 mg/kg /day) or combination therapy (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for another 6 weeks. Both treatments similarly reduced the blood pressure, improved survival and ameliorated LV enlargement. In contrast, several parameters of LV function were significantly ameliorated only by the high-dose ACE-I but not by the combination therapy. After the initiation of a relatively

Value of different clinical and biochemical correlates to assess angiotensin converting enzyme inhibition. In a double-blind study, we compared the value of different approaches to assess blockade of angiotensin (Ang) II generation in 10 normal volunteers treated with the new Ang-converting enzyme (ACE) inhibitor temocapril. Plasma concentration of the diacid active metabolite of temocapril , plasma Ang I and II levels, plasma ACE activity, and inhibition of the pressor response to repeated intravenous (i.v.) doses of Ang I were measured before and repeatedly after different doses of tempocapril or placebo. In vivo ACE activity, estimated by the plasma Ang II/Ang I ratio, correlated well with temocapril diacid concentration (r = 0.85, n = 148) and with systolic and diastolic blood pressure

Chronic treatment with an ACE inhibitor, temocapril, lowers the threshold for the infarct size-limiting effect of ischemic preconditioning. This study examined whether chronic inhibition of the angiotensin-converting enzyme (ACE) lowers the threshold of preconditioning (PC) and potentiates cardio-protection of subthreshold PC. Rabbits were orally administered either 0.5 mg/kg/day temocapril activity assay. There was no significant difference in %IS/AR among the rabbits given placebo alone, placebo plus 2 minutes PC, and temocapril alone (%IS/AR = 59.5 +/- 5.8%, 43.6 +/- 3.7%, and 56.7 +/- 7.1%, respectively). However, %IS/AR was significantly reduced in the group that received temocapril and 2 minutes PC before infarction (%IS/AR = 35.4 +/- 4.8%, P < 0.05 vs. placebo control and temocapril