Disease relevance of temocapril hydrochloride

• At 11 weeks, when these rats displayed compensated left ventricular hypertrophy (LVH), they were randomized to three groups: 1) IGF group (3 mg/kg/day); 2) temocapril group (1 mg/kg/day); and 3) vehicle (control) group [1].
• These observations suggest that temocapril is beneficial in the treatment of hypertension in patients with severely impaired renal function [2].
• In rats with experimental autoimmune myocarditis (EAM), the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21 [3].
• 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 [4].
• Pharmacokinetics of temocapril and enalapril in patients with various degrees of renal insufficiency [2].

High impact information on temocapril hydrochloride

• The survival time was significantly shortened (15.6+/-0.3 weeks) in the IGF-1 group but significantly prolonged (19.5+/-0.6 weeks) in the temocapril group [1].
• The alpha-MHC mRNA level was decreased by 52% (p<0.01) in the IGF group, while it increased by 58% (p<0.01) in the temocapril group compared with the control group [1].
• [Pro(11), D-Ala(12)]Ang I (10(-8) to 10(-5) mol/L), a chymase-specific substrate, provoked similar responses in rat and hamster arteries; chymostatin, but not temocapril, attenuated the responses [5].
• First, we examined the effects of the ACE inhibitor temocapril and the angiotensin II AT1 subtype receptor antagonist CS-866 on the structural remodeling induced by administering L-NAME for 8 weeks [6].
• In VSMC conditioned medium, FN-induced elevation of Ang II was significantly inhibited by temocapril but not by chymostatin [7].

Chemical compound and disease context of temocapril hydrochloride

• Effects of troglitazone and temocapril in spontaneously hypertensive rats with chronic renal failure [8].
• We studied an alteration of calcineurin expression in the heart and its modification by cyclosporin A and an ACE inhibitor, temocapril, using Dahl salt-sensitive (DS) rats with hypertensive left ventricular hypertrophy (LVH) and congestive heart failure (CHF) [9].
• These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans [10].
• Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not [10].
• Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy [11].

Biological context of temocapril hydrochloride

• Temocapril ameliorates myocarditis associated with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated [3].
• Coadministration of temocapril dose dependently improved both changes in blood pressure and the systemic HbNO concentration [12].
• RESULTS: Temocapril significantly prevented aortic dissection (P <.05), CMD (P <.01), and VSMC apoptosis (P <.01) compared with vehicle control in BAPN-fed rats [13].
• Hydrolysis experiments of temocapril in Caco-2 cell 9000g supernatant (S9) and brush-border membrane vesicles showed that temocapril was mainly hydrolyzed within the cells after uptake, after which the temocaprilat formed was transported to both the apical and basolateral surfaces [14].
• In contrast, chronic temocapril treatment (20 mg/kg/day) restored the downregulation of calcineurin expression, but progression of the hypertrophic process was inhibited [9].

Anatomical context of temocapril hydrochloride

• METHODS: 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 [15].
• The absorption characteristics of temocapril were investigated using Caco-2 cells, and the esterases expressed in Caco-2 cells were identified [14].
• The purified enzyme possessed temocapril hydrolase activity, and it was found to contribute significantly to temocapril hydrolase activity in mouse liver microsomes [16].
• A possible therapeutic role for temocapril in damaged motor neurons, such as in motor neuropathy and amyotrophic lateral sclerosis, remains to be defined [17].
• Influence of temocapril on cultured ventral spinal cord neurons [17].

Associations of temocapril hydrochloride with other chemical compounds

• At the age of 10 weeks, the rats were randomly allocated to groups that received troglitazone (70 mg/kg per day); the angiotensin converting enzyme inhibitor temocapril (10 mg/kg per day); troglitazone (70 mg/kg per day) plus temocapril (10 mg/kg per day), or a vehicle alone as an untreated control group [8].
• Blood pressure was significantly and equally lowered in both temocapril and CS-866 groups compared with control [13].
• The pharmacokinetics of temocaprilat, an active metabolite of temocapril, did not differ significantly between the two dosing times [18].
• Rabbits with MI were randomized to no treatment, the ACE inhibitor temocapril (0.5 mg/kg/day) or AT1 receptor blocker valsartan (3 mg/kg/day) [19].
• Blood pressure was similarly decreased by treatment with temocapril or amlodipine [10].

Gene context of temocapril hydrochloride

• Genetically obese ob/ob mice were given ACE inhibitor (temocapril) or Ang II type 1 (AT(1)) receptor blocker (olmesartan) from 10 to 20 weeks [20].
• Conversely, in vivo experiments revealed that administration of temocapril and CS-866 to cardiomyopathic hamsters resulted in a significant decrease in fibrotic area and increase in cardiac HGF concentration and mRNA (P<0.01), whereas cardiac concentration and mRNA of HGF were significantly decreased in cardiomyopathic hamsters [21].
• The antihypertensive effect of temocapril was greater in aged eNOS mice, associated with reduction in the ventricular weight in both strains [22].
• Three-day treatment with CS866, an AT1 receptor antagonist, and temocapril, an angiotensin-converting enzyme inhibitor, suppressed AT1 receptor expression in the rat adrenal cortex, but not in the heart or adrenal medulla [23].
• In temocapril-treated VSCC, choline acetyltransferase (ChAT) activity was also increased 2.4-3.2 times over that of control at 10(-9) and 10(-8) M, respectively [17].

Analytical, diagnostic and therapeutic context of temocapril hydrochloride

• Furthermore, high doses of CS-866 or temocapril treatment significantly reduced the positive stainings for transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, and type IV collagen in glomeruli of diabetic rats [24].
• Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment) [25].
• Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was increased by the preconditioning treatment [26].
• Chronic treatment with an ACE inhibitor, temocapril, lowers the threshold for the infarct size-limiting effect of ischemic preconditioning [27].
• In a prospective randomised cross-over study, we compared the effects of ACE inhibitor temocapril and calcium channel blocker (CCB) amlodipine on ambulatory blood pressure in 59 asymptomatic elderly hypertensive patients (mean age 69 years) [28].

References