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Objective To investigate the effects of cilazapril on heart rate corrected QT interval disoersion (QTcd) and ventricular arrhythmia (VA) in patients with essential hypertension. Methods 96 hypertensive patients with LVH were divided randomly into two groups. 48 patients in lercanidipine group were treated routinely plus lercanidipine. 48 patients in cilazapril group were treated with routine drugs plus cilazapril. QTcd of 12-lead sur-face ECC and VA malignant degree recorded by Holter were analyzed before therapy and 6 mgnths after therapy. Re-suits In the cilazapril group,the QTcd was different before and after the therapy ((76±12) ms vs (65±9) ms, P<0.05 ). In the lercanidipine group, the QTcd was not significantly different ((76±13 ) ms vs (74±12) ms, P > 0.05). QTed and the malignant degree of VA between the two groups were significantly different after the therapy. Conclusions Treatment with cilazapril can reduce the QTcd and the malignant degree of VA in hypertensive patients with LVH.
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Thirty seven patients with congestive heart failure (CHF) were divided into cilazapril group (n=19) and general treatment group (n=18). Serum levels of interleukin-6 (IL-6) ,interleukin-8 (IL-8) , interleukin-10(IL-10) and tumor necrosis factor-α(TNF-α) , left ventricular ejection fraction (LVEF) ,left ventricular end-diastolic diameter (LVEDD), cardiac output (CO) and fractional shortening (FS) were measured before and after treatment. Serum levels of cytokines were also measured in 40 healthy individuals (control group). Results: The serum levels of IL-6, IL-8, IL-10 and TNF-α in CHF patients were significantly higher than those in the control group ( all P<0.01 ) ; After treatment, the serum IL-6, IL-8 and TNF-α were significantly decreased (P<0.01 ,P<0.05 ) in the cilazapril group. The LVEF, FS, CO were significantly increased in the Cilazapril group ( P<0.01 ) ; And the serum levels of IL-6 were significantly decreased in the cilazapril group as compared with the general treatment group ( P<0.05 ), however, after treatment, the EF, LVEF, FS and CO had no statistical differences in the cilazapril group as compared with the general treatment group. In the control group only LVEF and FS improved(P<0.01) ; Cytokine levels showed no changes. It suggests that cilazapril can reduce the serum levels of pro-inflammatory cytokines, increased the serum levels of anti-inflammatory cytokine, protect and improved cardiac function in the patients with congestive heart failure.
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Objective To observe endothelial and fibfinolytic functions of clinical AF patients and effects of cilazapril on it and to investigate the mechanism and treatments of thrombogenesis in AF.Methods 63 AF patients were randomly di- vided into control group (n=30) and cilazapril group (n=33).All patients received general treatment according symptoms.In addition,the patients in cilazapril group received cilazapril (2.5mg/d,2 weeks).Plasma Ang Ⅱ, vWF,t-PA and PAI-1 level were measured before and after 2 weeks.There were 36 patients with sinus rhythm (SH) in non-AF control group.Results AF patients had higher plasma AnglI level than SH patients that indicated RAS acti- vated[(107.7?22.0) ng/L vs (70.2?15.8) ng/L,P
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Objective To observe endothelial and fibrinolytic functions of clinical AF patients and effects of cilazapril on it and to investigate the mechanism and treatments of thrombogenesis in AF.Methods 63 AF patients were randomly divided into control group(n=30)and cilazapril group(n=33).All patients received general treatment according symptoms.In addition,the patients in cilazapril group received cilazapril(2.5mg/d,2 weeks).Plasma Ang Ⅱ, vWF,t-PA and PAI-1 level were measured before and after 2 weeks.There were 36 patients with sinus rhythm (SH)in non-AF control group.Results AF patients had higher plasma Angll level than SH patients that indicated RAS activated[(107.7?22.0)pg/mL vs(70.2?15.8)pg/mL,P
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Objective To explore the effects of simvastatin and cilazapril on the expression of transforming growth factor-?_1 (TGF-?_1) and insulin-like growth factor-Ⅰ (IGF-Ⅰ) in the cultured human glomerular mesangial cells. Methods Human embryo glomerular mesangial cells were cultured in media with lower (5.6 mmol/L) or higher (30 mmol/L) glucose concentrations. Forty-eighthoursafteraddingsimvastatin(10 ?mol/L)and/or cilazapril (10 ?mol/L) to the cultured media, the concentrations of TGF-?_1, fibronection, laminin, type Ⅳ collagen proteins in the supernatant of cultured mesangial cells were determined by ELISA and radioimmunoassay and the expressions of TGF-?_1 and IGF-Ⅰ mRNA in cultured mesangial cells were also evaluated by RT-PCR. Results Compared with lower glucose control, the mesangial cells in the medium with higher glucose concentration showed excessive proliferation and higher expressions of TGF-?_1 and IGF-Ⅰ mRNA, and the levels of TGF-?_1, fibronection, laminin, and type Ⅳ collagen in the supernatant were also significantly increased. The expressions of TGF-?_1 and IGF-Ⅰ mRNA in the mesangial cells and the concentrations of TGF-?_1 and the extracellular matrix (ECM) proteins in the supernatant were all decreased after addition of simvastatin and cilazapril. Combination of simvastatin and cilazapril resulted in more profound suppressive effect on the expression of TGF-?_1 mRNA than either of them alone. Conclusion High concentration of glucose stimulates the cultured human mesangial cells excessively to express the TGF-?_1, IGF-Ⅰ and ECM proteins, and the high glucose-induced changes are suppressed by either simvastatin, cilazapril alone or combined treatment.
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AIM: To study the effect of cilazapril on pulmonary vascular endothelial dysfunction in hypoxic rats. METHODS: The structure and function of endothelium in hypoxic rats were studied by biochemical analysis, radioimmunoassay, transmission electron microscope and correlated with hemodynamic. RESULTS: 1) The change and damage of ultrastructure in endothelial cell (EC) were obsevered in hypoxic rats. 2) The contents of plasma nitric oxide (NO) and superoxide dismutase (SOD) activity in blood as well as endothelial nitric oxide synthase (eNOS) activity in the lung tissue were significantly lower in the hypoxic rat than those in contral animals. The concentrations of plasma endothelin-1(ET-1) and angiotensin converting enzyme(ACE) as well as malondialdehyde(MDA) were significantly higher in the hypoxic rat than these in contral animals. The relaxing and contracting factors had a significant positive/negative correlation with mean pulmonary artery pressure (mPAP). 3) Cilazapril significantly decreased the level of ET-1 and ACE and significantly increased the level of NO and activity of eNOS and SOD. At the same time, cilazapril extenuated hypoxia-induced injuries of EC. CONCLUSION: The results indicate that damaging structure and dysfunction of EC existes in hypoxic rats. The cilazapril effectively preventes and treates the chronic hypoxic PH by relieving the injury and improving secretion in EC.
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0 05) Left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all higher and left ventricular pressure maximal rate of rise and fall (?d p /d t ) were lower (all P
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group A by turns. (3) The concentrations of plasma endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) were significantly higher in group B than that in group A. However, the ET-1 and ACE were significantly lower in group C than those in group B. (4) The ET-1 and ACE had a significant positive correlation with R/L+S, mPAP and PI, respectively. The multivariate linear regression analysis revealed that ET-1 and ACE were major factor affecting PI. CONCLUSION: The pulmonary vascular and myocardial structural remodeling are one of the pathogenesis accompanied with excessive cell proliferation in hypoxic pulmonary hypertension (PH). Cilazapril effectively prevents and treats the hypoxic PH by inhibiting cell proliferation and structural remodeling of pulmonary circulation, as induced by ET-1 and ACE.
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BACKGROUND AND OBJECTIVES: Angiotensin converting enzyme inhibitor (ACEI) is known to be effective in the prevention of left ventricular failure (LVF) after acute myocardial infarction. The aim of this study was to investigate the efficacy of an ACEI, Cilazapril, on left ventricular remodeling in patients with ischemic LVF, who underwent coronary interventions. MATERIALS AND METHODS: Cilazapril, 2.5 - 5.0 mg per day was administ-ered 12 weeks after coronary interventions in 25 patients (18 M, 7 F, 61.5+/-9 years) with impaired LV function (ejection fraction< or = 50%). Fifteen patients (9 M, 6 F, 59.4+/-7 years) without ACEI were compared by clinical examinations, blood chemistry, electrocardiogram and echocardiogram with Cilzapril group at 2, 4, 8 and 12 weeks after intervention. RESULTS: Blood pressure and heart rate were not changed after Cilazapril. LV end-diastolic volume (LVEDV) decreased from 153.1+/-38.7 to 135.6+/-25.5 ml and end-systolic volume from 84.9+/-34.7 to 72.6+/-25.1 ml after 12-week Cilazapril p=0.003, p=0.001. Ejection fraction (EF) was increased from 44.4+/-3.2 to 52.4+/-2.8% after 12 weeks of Cilazapril p=0.034. In control group, LVEDV was changed from 152.7+/-44.6 to 143.6+/-28.7 ml, which failed to show significant reduction. Side effects of Cilazapril were 3 dry cough (3/25, 12%) and 1 facial edema, 1 hypotension and 1 dizziness. CONCLUSION: Cilazapril is a beneficial adjunctive therapeutic agent in patients with ischemic left ventricular failure for the prevention of ventricular dilatation, especially after coronary intervention.
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Humans , Blood Pressure , Chemistry , Cilazapril , Cough , Dilatation , Dizziness , Edema , Electrocardiography , Heart Failure , Heart Rate , Heart , Hypotension , Myocardial Infarction , Peptidyl-Dipeptidase A , Ventricular RemodelingABSTRACT
PURPOSE--To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. METHODS--forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmHg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. RESULTS--The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 +/- 14/103 +/- 5 - nifedipine 157 +/- 17/108 +/- 7mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 +/- 9 - nifedipine 96 +/- 11mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no difference inter groups. BP normalization was obtained in 58 per cent of the patients with cilazapril and in 61 per cent in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16 per cent) patients of the cilazapril and 15 (39per cent) of nifedipine related collateral events, although no difference were observed between groups. CONCLUSION--Cilazapril 2.5 to 25mg normalized BP in 58 per cent of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects
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Humans , Male , Female , Adult , Middle Aged , Nifedipine/administration & dosage , Cilazapril/administration & dosage , Hypertension/drug therapy , Time Factors , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Nifedipine/adverse effects , Treatment Outcome , Cilazapril/adverse effects , Hypertension/physiopathology , Double-Blind Method , Arterial PressureABSTRACT
PURPOSE--To evaluate the tolerability and 24 hours efficacy of a new anti-hypertensive drug: cilazapril. METHODS--In an open non comparative study 20 hypertensive patients (16 females, age from 30 to 60 years, average = 49.4) were followed for 6 weeks: 2 wash out and 4 treatment (5 mg OD). Blood pressure (BP) was measured by casual and ambulatory blood pressure monitoring (ABPM) readings. RESULTS--Comparing washout and treatment periods, ABPM averages both for systolic and diastolic BP (mmHg) showed significant decrease in 24 hours, during day and night sub periods. The decrease was not significant between averages considering the early morning rising pressure sub period. Heart rate averages showed significant reduction at all sub periods except during night. Adverse effects were mild and resolved spontaneously (n = 3, 15 per cent ). CONCLUSION--Cilazapril seems to be efficacious as antihypertensive. Tolerability is excellent. It preserved circadian rhythm despite significantly reducing blood pressure at all periods evaluated except early morning. A bradycardic effect observed mostly during day period should be better evaluated
Objetivo - Avaliar a tolerabilidade e eficácia antihipertensiva nas 24h do novo inibidor da ECA: cilazapril. Métodos - Num estudo aberto e não comparativo foram avaliados 20 pacientes (16 mulheres, idade entre 30 e 60 (média 49,4) anos, durante 6 semanas (2 de wash out e 4 de tratamento: cilazapril 5mg OD). A pressão arterial (PA) foi avaliada por método casual e por monitorização ambulatorial da pressão arterial (MAPA). Resultados - As médias de MAPA, comparando as fases pré droga e com droga, mostraram que tanto para pressão arterial sistólica (PAS) como diastólica (PAD), houve significativa redução de cifras, nas 24h, no período do dia e no da noite. Não houve redução significativa no sub-período da "ascensão rápida da PA " no fim da madrugada. A freqüência cardíaca média mostrou redução quando comparadas as médias das 24h e do dia, sem significância estatística nos demais sub-períodos. Os efeitos adversos foram leves e resolveram espontaneamente (n=3,15%). Conclusão - O cilazapril parece ser um eficaz anti-hipertensivo. A tolerabilidade foi excelente. Houve preservação do rítmo circadiano apesar da significativa redução das cifras tensionais em todos os períodos avaliados exceto o início da manhã (ascensão rápida da PA). Um discreto efeito bradicárdico notado durante o dia precisa ser melhor observado.
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Humans , Male , Female , Adult , Middle Aged , Cilazapril/therapeutic use , Ambulatory Care , Arterial Pressure , Electrocardiography, Ambulatory , Circadian Rhythm/drug effects , Heart Rate , Hypertension/drug therapyABSTRACT
BACKGROUND: In order to investigate the efficacy and safety of cilazapril, a recently developed angiotensin converting enzyme inhibitor, a clinical study was performed in the patients with mild to moderate essential hypertension. METHODS: The study subject consisted of 31 patients with diastolic blood pressure of 95mmHg~115mmHg (mean age : 56.0+/-8.1 years, 16 males and 15 females). Cilazapril was administered orally in a daily dose of 2.5mg~5.0mg Q.D. for 8 weeks. During cilazapril medication, anti-hypertensive efficacy, side effects and laboratory changes were monitored. RESULTS: Cilazapril decreased blood pressure from baseline value of 162.2+/-4.7/98.4+/-2.8mmHg to 144.6+/-10.0/89.7+/-5.7mmHg after 4weeks of medication (p<0.05) and 138.2+/-4.5/87.8+/-4.0mmHg after 8 weeks of medication (p<0.05). Heart rate change was not significant (72.3+/-4.7/min vs 71.7+/-3.6/min). Body weight change was not significant (66.6+/-9.8 Kg vs 66.8+/-9.9 Kg). There were no significant change in blood chemistry and hematologic examination except mild elevation of alanine transaminase and serum creatinine values but these date were within normal ranges. The side effects were dry cough (4 case, 12.9%), headache (2 case, 6.4%), indigestion (1 case, 3.2%) and dry mouth (1 case, 3.2%). One patient dropped out due to severe dry cough but others were mostly mild in nature. CONCLUSIONS: Cliazapril 2.5mg~5.0mg once daily regimen was effective and well tolerated in patients with mild to moderate essential hypertension.
Subject(s)
Humans , Male , Alanine Transaminase , Blood Pressure , Body Weight Changes , Chemistry , Cilazapril , Cough , Creatinine , Dyspepsia , Headache , Heart Rate , Hypertension , Mouth , Peptidyl-Dipeptidase A , Reference ValuesABSTRACT
A double-blind study of cilazapril (ACE inhibitor) versus nifedipine retard (calcium antagonist) in the treatment of 18 (10 on cilazapril and 8 on nifedipine) mild to moderate essential hypertensive patients (diastolic B.P. 95-115 mmHg) was performed. Both drugs were effective in lowering blood pressure to satisfactory levels by using cilazapril 2.5-5 mg once daily and 20 mg twice a day of nifedipine retard for 10 weeks. There were no adverse effects on hematological or biochemical parameter studies and no other side-effect, especially cough which is usually attributed to the ACE inhibitor therapy. This study showed that cilazapril, a new once daily ACE inhibitor, and nifedipine are safe and effective antihypertensive agents.
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In order to investigate the efficacy and safety of oral cilazapril, a new angiotensin converting enzyme inhibitor, on essential hypertension, a single daily dose of 2.5 to 5.0mg cilazapril was administered in 30 hypertensive patients with diastolic blood pressure in the range of 95??15mmHg while off all other anti-hypertensive agents for 10 weeks. Blood pressure and heart rate were measured every 2 weeks. The complete blood count with platelet count, blood chemistry by SMA-12 including lactic dehydrogenase and serum electrolytes, and urinalysis were performed at 4th and 10th week of therapy. The electrocardiography was performed at the beginning and the end of treatment period. Any kinds of side effects were actively questioned by the examining physicians. The following results were obtained : 1) The mean age was 49.2 years, and the ratio of male-to-female was 1 : 1.3. 2) Blood pressure started to fall significantly within 2 weeks of treatment with cliazpril 2.5mg(M+/-S.E., 15.4+/-17.4mmHg vs 138.5+/-23.3, 100.3+/-6.2 vs 89.4+/-6.6, p0.05). 4) There were no significant changes in blood chemistry including blood sugar, cholesterol and electrolytes, except mild changes of serum creativine and alkaline phosphatase values. 5) Hematologic findings, urinalysis and electrocardiographic findings remained unchanged. 6)Side effects were mostly mild in nature without potentially serious episodes(dry cough : 20%, indigestion, headache, dizziness, in order), but there was 1 cases in whom the dosage was redyced due to postural hypotension. From the above results, cilazapril with the dosage of 2.5 to 5.0mg was effectvie and well tolerated in essential hypertensive patients with diastolic blood pressure of 95 to 115mmHg, and cilazapril seems to be appropriate for monotherapy of mild to moderate hypertensive patients.