Blood pressure and cardiorenal responses to antihypertensive therapy in obese women

OBJECTIVE: Blood pressure(BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS: 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements - 37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS: After 24 weeks, weight loss was less than 2 percent in both groups. ABPM targets were achieved in 81.5 percent of patients upon a combination of 2(26.5 percent) or 3(55.1 percent) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity) / -23.6/-14.9mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS: In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.

As respostas pressórica e de órgãos-alvo mediante o tratamento anti-hipertensivo medicamentoso, não estão bem estabelecidas em pacientes obesos hipertensos. O presente estudo tem por objetivo avaliar as repercussões da obesidade e da distribuição de gordura corporal sobre estas respostas. MÉTODOS: Foram avaliadas 49 mulheres obesas hipertensas, separadas em subgrupos com distribuição troncular (n = 37) e periférica (n = 12) de gordura, de acordo com a distribuição cintura/quadril. As pacientes foram tratadas por 24 semanas com um regime anti-hipertensivo escalonado, iniciando-se com cilazapril e adicionando-se na seqüência, hidroclortiazida e amlodipina, com alvo pressórico inferior a 140 x 90 mmHg. Foram realizados MAPA, ecocardiograma e microalbuminuria antes e após o tratamento. RESULTADOS: Depois de 24 semanas observou-se perda de peso inferior a 2 por cento em ambos os subgrupos. O controle pressórico à MAPA pode ser observado em 81,5 por cento das pacientes mediante a combinação de duas (26,5 por cento) ou três (55,1 por cento) drogas. Foram obtidas reduções similares nas medidas de PAS/PAD diurnas: -22,5/-14,1(obesas tronculares)/-23,6/-14,9 mmHg (obesas periféricas), enquanto se observou nas obesas tronculares redução maior na PAS noturna. Mediante o controle pressórico, houve redução acentuada da microalbuminúria nos dois subgrupos. Por outro lado, observou-se em ambos, apenas discreta redução na massa ventricular. CONCLUSÕES: Na ausência de perda significativa de peso, e independentemente da distribuição de gordura corporal, a maioria das pacientes obesas necessitou terapia anti-hipertensiva combinada a fim de obter controle pressórico. Em ambos os subgrupos foram alcançados níveis adequados de pressão arterial e redução satisfatória da microalbuminúria, ao passo que os benefícios para a regressão estrutural cardíaca foram menores.

Análisis del costo efectividad de dos inhibidores de la ECA en el manejo de la hipertensión arterial primaria: Cilazapril (inhibace TM) vs Captopril (Genérico) en un modelo institucional / Cost effectiveness analysis of two ECA inhibitors in the management of primary arterial hypertension. Cilazapril (inhibace TM) vs generic captopril in an institutional model

El propósito de este estudio fue efectuar una evaluación fármaco económica de la terapia para la Hipertensión Arterial (HTA) con dos inhibidores de la ECA; el Cilazapril y el captopril, considerando el costo integral de cada uno, es decir, costos pagados más ahorros generados por la reducción del número de complicaciones como consecuencia de una adecuada administración del tratamiento y mejor adherencia a uno de los dos fármacos. En el Sistema Peruano de Seguridad social, aún no se diferencian estos costos y por ello, las decisiones de inversión consideran unicamente el efecto de los precios y su impacto a corto plazo. El resultado del estudio muestra que el costo anual del tratamiento integral con dosis única de 5mg de Cilazapril es de S/ 8,201 mientras que el costo de tratarlo con 3 dosis de 25 mg de Captopril es de S/ 9,495 dado que la adherencia al tratamiento es distinta (86 por ciento para la monodosis vs. 50 por ciento para 3 tomas al día). El análisis costo / efectividad anualizado, muestra adicionalmente que para mantener a un paciente debidamente adherido y controlado, es necesario invertir S/. 16,441 con Cilazapril ó S/. 32,741 con Captopril. Este análisis fármaco económico lleva a la conclusión que el manejo de la HTA no se puede basar sólo en el precio del medicamento, puesto que con ello se perdería la perspectiva del horiizonte temporal del tratamiento y se omitiría considerar el cálculo del costo de las complicaciones asi como el ahorro que se puede generar con una mejor adherencia y control de la HTA.

Effect of Cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation models / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation (AF) models.</p><p><b>METHODS</b>All canines were divided into three groups: (1) Control group, without atrial pacing; (2) Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks; (3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay.</p><p><b>RESULTS</b>NO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group [(42.6 +/- 9.9) nmol/L vs (23.4 +/- 5.8) nmol/L, P < 0.05], whereas the plasma levels of vWF were decreased [(75.4 +/- 12.8)% vs (125.9 +/- 20.6)%, P < 0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052 +/- 857 vs 1936 +/- 421, P < 0.05) and PAI-1 protein was downregulated (2487 +/- 542 vs 3164 +/- 827, P < 0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma.</p><p><b>CONCLUSION</b>Cilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.</p>

Effects of Renin-angiotensin System Blockade on Tubulointerstitial Lesions in Adriamycin-induced Nephropathy / 대한신장학회잡지

PURPOSE: Effects of renin-angiotensin system blockade on tubulointerstitial lesions were examined in adriamycin-induced nephropathy. METHODS: Male Sprague-Dawley rats were used. The three experimental groups were intravenously injected with adriamycin (2 mg/kg). After 6 weeks, rats showing heavy proteinuria were orally treated with either cilazapril 1 mg/kg/day (ACEi group, n=7) or losartan 10 mg/kg/day (ARB group, n=7) during the period of additional 6 weeks. The other group was maintained without any drugs (ADR group, n=6). The control group was without adriamycin treatment and maintained during the 12 weeks (Control, n=5). RESULTS: Systolic blood pressure was increased following the adriamycin treatment, which was normalized by treatment with cilazapril or losartan. Accordingly, cilazapril and losartan normalized the 24-h urine protein/creatinine ratio, in association with morphologic improvement of tubulointerstitial lesions. The expression of laminin beta1 was not altered in any experimental groups. CONCLUSION: These results suggest that angiotensin II plays an important role in tubulointerstitial lesions in adriamycin-induced nephropathy.

Eficacia antihipertensiva y tolerabilidad de cilazapril más hidroclorotiazida en el perfil de presiones arteriales ambulatorias de 24 horas / Antihypertensive efficacy and tolerability of cilazapril plus hydrochlorotiazide, in the blood pressure measurement with ambulatory blood pressure

El efecto de cilazapril, un inhibidor de la enzima convertidora de la angiotensina ha sido estudiado durante las 24 h en muchos trabajos. Sin embargo, no se conocen sus resultados sobre los Indices de Homogeneidad (IH)ni su acción durante el período 6 am a 12 am en que se produce un porcentaje importante de las complicaciones cardiovasculares de la hipertensión arterial. Objetivo: Estimar la disminución de las PA con cilazapril más HCT y conocer los IH durante el día, la noche y desde las 6 am a las 12 am por medio del MAPA de 24 h y comparar estos resultados con el T/R ratio. Material y método: en un estudio no comparativo se evaluó el efecto antihipertensivo de cilazapril en dosis crecientes de 2,5,5 y 7,5 mg más 12,5 mg de HCT en 24 pacientes con hipertensión arterial esencial con edad media de 49 ±8 años hasta lograr el efecto máximo a las 12 semanas y realizar el segundo MAPA de 24 h. Resultados: Cilazapril en dosis promedio de 5 ±1,8 mg más 12,5 mg de HCT redujo en forma significativa p<0,001 las PAS y PAD en todos los períodos de las 24 h. Durante el día las PA promedio obtenidas fueron 125/83 mm Hg y en la noche 114/75 mm Hg. Las reducciones medias horarias del día fueron para la PAS de 25 ±16mm Hg y de la PAD DE 17 ±7 mm Hg. Durante la noche la disminución fue para la PAS de 18 ±14 mm Hg y para la PAD de 10 ±9 mm Hg. Los IH fueron durante el día, el sistólico de 1,74 ±1,19 y el diastólico de 1,75 ±0,98 y durante la noche, el sistólico de 1,70 ±1,11 y el diastólico de 1,29 ±1,13. En las 24 h el IHS fue de 1,47 ±0,89 y el IHD de 1,32 ±0,6. En el período crítico de 6 am a las 12 am las PAS se reducen en 23 mm Hg y las PAD en 15 mm Hg. Los IH en este período fueron: IHS: 1,88 ±1,5 y el IHD. 1,86 ±1,10. El T/P sistólico fue de 69 ±20 y el diastólico de 64 ±20. Sólo los IH se correlacionaron significativamente con sus respectivas reducciones de PA. Conclusión: Cilazapril en pacientes hipertensos esenciales estudiados con el MAPA de 24 h con dosis 5 ±1,8 mg más 12,5 mg de HCT redujo en forma significativa p<0,001 las PAS y D durante el día y la noche. La disminución fue homogénea y sostenida corroborada por el estudio de los IH durante el día, noche y desde las 6 am hasta las 12 am.

Angiotensin converting enzyme inhibitor induced cough: experience in Siriraj Hospital.

With the increasing use of angiotensin converting enzyme inhibitors (ACEI) in the treatment of hypertension, particularly in diabetic patients, and heart failure, an annoying cough has frequently been observed. According to the post marketing surveillance studies, the prevalence of cough associated with ACEI was only 0.1-4 per cent. However, many recent studies have observed a very much higher frequency. To examine the incidence and pattern of cough associated with the usage of ACEI (C-ACEI) in a Thai population, mixed retrospective and prospective studies were performed in hypertensive patients who attended the out-patient department, Siriraj Hospital between December 1999 and August 2000. A thousand cases who had used or have been using ACEI were studied. C-ACEI was present in 179 cases of 760 retrospective studied cases (23.6%) and 75 cases of 240 prospective studied cases (31.3%). Cough was typically described as irritative (93.8% retrospectively and 98.7% prospectively, p = 0.05) and nocturnal in onset (74.9% retrospectively and 80% prospectively, p = 0.12), and usually appeared within the first 4 weeks of treatment (41.3% retrospectively and 46.7% prospectively, p = 0.43). Patients who received a full dosage of ACEI did not have to posses an increasing risk of C-ACEI. There was no difference in the prevalence of C-ACEI among types of ACEI, except cilazapril and quinapril which were found to be higher than enalapril in the retrospective study (p < 0.0001 and p = 0.002, respectively). Types of study were shown to influence the prevalence of C-ACEI. Prospective studies yielded a higher rate of C-ACEI than retrospective ones.

Changes in Laminin beta 1 Chain Expression in Renal Cortex by the Intervention with Cilazapril and Losartan on Adriamycin-Induced Nephropathy / 대한해부학회지

Laminin, an extracellular matrix glycoprotein, is distributed in the basement membrane of renal glomerulus. Laminin has been demonstrated to regulate the development and differentiation of glomeruli and play an important role in the filtering function of glomeruli. To address whether laminin beta 1 chain is associated with the pathogenic states of renal injury and recovery, nephropathy were induced by intravenous adriamycin injection and subsequently cured by treatment with antihypertensive drugs, cilazapril (angiotensin-converting enzyme inhibitor, ACEi) and lozartan (angiotensin receptor blockade, ARB), which have been known to be effective on renal protection. The results we obtained were as follows: 1. At 6 and 12 weeks after adriamycin injection, epithelial cells of proximal convoluted tubules exhibited intensive deposition of laminin beta 1 chain reactive gold particles. Cytoplasm of podocytes and mesangial cells in glomeruli showed an increase in the gold particle deposition as compared with that of controls. The mRNA level of laminin beta 1 chain was enhanced in the epithelial cells of proximal convoluted tubules. 2. Following cilazapril administration to adriamycin -induced nephropathy rats, laminin beta 1 chain reactive gold particle deposition was reduced in the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. The level of laminin beta 1 chain transcripts was remarkably decreased in the epithelial cells of proximal convoluted tubules. 3. Following losartan administration to adriamycin -induced nephropathy rats, podocytes and mesangial cells were deposited with reduced number of laminin beta 1 chain reactive gold particles. The laminin beta 1 chain reactive gold particles and level of laminin beta 1 chain mRNA transcripts were remarkably reduced in the epithelial cells of proximal convoluted tubules. 4. Treatment with mixture of cilazapril and losartan to adriamycin -induced nephropathy rat resulted in a decrease in laminin beta 1 chain reactive gold particle deposition within the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. Laminin beta 1 chain mRNA expression in the epithelial cells of proximal convoluted tubules nearly disappeared. These results consequently suggest that laminin beta 1 chain may be synthesized within the epithelial cells of proximal convoluted tubules, podocytes and mesangial cells and laminin beta 1 chain may play an important role on tissue recovery of the renal tissues injured by adriamycin.

Upregulation of Renal Renin-Angiotensin System in Rats with Adriamycin-Induced Nephrosis

The present study was aimed to investigate whether the adriamycin-induced nephrosis is associated with an altered regulation of local renin-angiotensin system (RAS) in the kidney. Rats were subjected to a single injection of adriamycin (2 mg/kg body weight, IV) and kept for 6 weeks to allow the development of nephrosis. They were then divided into two groups, and supplied with and without cilazapril, an angiotensin converting enzyme (ACE) inhibitor, in drinking water (100 mg/l) for additional 6 weeks. Another group without adriamycin-treatment served as control. The mRNA expression of renin, ACE, type 1 and type 2 angiotensin II receptors (AT1R, AT2R), and transforming growth factor (TGF) -beta1 was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. Adriamycin treatment resulted in heavy proteinuria. Accordingly, the mRNA expression of renin, ACE, and AT1R was increased in the renal cortex, while that of AT2R was decreased. Co-treatment with cilazapril attenuated the degree of proteinuria. While not affecting the altered expression of renin, cilazapril decreased the expression of ACE to the control level. Cilazapril further increased the expression of AT1R, while it restored the decreased expression of AT2R. The expression of TGF-beta1 was increased by the treatment with adriamycin, which was abolished by cilazapril. An altered expression of local RAS components may be causally related with the development of adriamycin-induced nephrosis, in which AT1R is for and AT2R is against the development of nephrosis.

Effects of ACE-I on diabetic cardiovascular complications: anti-hypertensive and non-antihypertensive doses.

To evaluate the effects of angiotensin converting enzyme inhibitor (ACE-I) on diabetic cardiovascular complications, a streptozotozin (STZ, i.p., 70 mg/kg BW) induced diabetes rat model was used. The animals were separated into four major groups including: control (NSS), STZ-treated rats, STZ-treated rats received daily oral feeding of cilazapril starting one day after STZ injection (STZ-C1), and STZ-treated rats received daily oral feeding of cilazapril eight weeks after the STZ injection (STZ-C8). Within the groups of STZ-C1 and STZ-C8, the animals were also divided into three subgroups of six rats that received different doses of cilazapril treatment, 0.01 mg/Kg BW, 1 mg/Kg BW, and 10 mg/Kg BW. By using the modified isolated heart model, the parameters of mean arterial pressure (MAP), heart rate (HR), left ventricular isotonic contraction (LVIC), aortic flow rate (AFR), coronary flow rate (CFR), and ratio of heart weight per body weight (R) were assessed for each groups 8 and 20 weeks after the STZ injections. Moreover, the changes of wall thickness of the left ventricular wall (LV), right ventricular wall (RV), and interventricular septal wall (IVS) were monitored from the scanning electron micrographs of each heart. The results indicated that in both STZ-C1 and STZ-C8, the diabetic hypertension could be prevented or treated by anti-hypertensive doses of cilazaprils. Besides, the values of AFR, CFR, and LVIC were significantly increased when comparing between the STZ and STZ-C1 or STZ-C8. The results of morphological examinations indicated that: (1) left ventricular walls of the three hearts of STZ-rats had increased significantly more than controls. (2) Right ventricular walls and interventricular septal walls were not significantly different among STZ-rats, cilazapril treated STZ-rats and age matched controls. Therefore, it is concluded that ACE-I could act either as a cardioprotective or therapeutic agent for diabetic hearts. Both major anti-hypertension and anti-trophic effects of ACE-I have already been elucidated.

Measurement of glomerular filtation rate under cimetidine and ACE inhibitor [cilazapril] in renal transplant patients

To ameliorate the performance of serum creatinine [SCr] as an estimate of glomeular filtration rate [GFR] and functioning renal mass by blocking secretion with Cimetidine and limiting hyperfiltration with Cilazapril. Twenty renal transplant patients [mean age 37.5 years] with a stable renal function were divided into 2 groups [s. creatinine 1.2 mg]. Baseline renal function was measured by serum creatinine, creatinine clearance [CrCI], Cr51EDTA and repeated 48 hours after Cimetidine 2000 mg/day. The tests were performed again 15 days after the administration of Cimetidine and Cilazapril 2.5 mg/d. As expected SCr rose moderately when tubular secretion was blocked with Cimetidine. Cilazapril, however, failed to induce any modification in SCr, CrCI or Cr51EDTA clearance. In early renal failure, SCr is still an acceptable estimate of GFR in most patients. Cilazapril did not result in significant reduction in GFR [at least acutely]. Long term follow-up is required to verify this point and to demonstrate any additional beneficial effect

The effects of antiproliferative drugs at stenotic area associated with primary atherosclerotic lesions in apoE knockout mouse - Change of vascular remodeling

Apolipoprotein (apo) E deficient mouse can produce reproducible fixed stenotic primary atherosclerotic lesion, which reveals failure to remodel of vascular lumen, in the ascending aorta, external carotid, common carotid, iliac, femoral and popliteal arteries. To evaluate the effect of drugs in regarding to both prevention of primary atherosclerotic lesion and vascular remodeling, a systematic analysis of distribution of atherosclerotic lesions was undertaken in chow-fed, 9-momth-old apo E deficient mice, which was administrated drugs including asprin, methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) for 7 month from 3 month-old. On gross and microscopic examination, formation of primary atheroscleotic lesions could be delated and/or prevented patially by effets of these drugs. On morphometric examination, failure to remodel forming vascular stenosis could not be seen, though relatively mild atherosclerotic lesion occured at vascular tree. These data suggest that the stenotic process in advanced atherosclerotic vessels can be delayed and/or prevented by several drugs including methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) in vivo state.

Apnéia obstrutiva do sono e hipertensão arterial sistêmica / Obstrutive sleep apnea syndrome and hypertension

Hipertensão arterial sistêmica ocorre em 40 por cento a 90 por cento dos pacientes com síndrome de apnéia do sono tipo obstrutivo (SASO). A SASO, por sua vez, é encontrada em um terço dos pacientes previamente diagnosticados como tendo hipertensão essencial. O tratamento da SASO nestes casos leva à melhora da hipertensão. A fisiopatologia subjacente ao desenvolvimento de hipertensão pela SASO, inicialmente durante o sono e gradualmente acometendo o período de vigília envolve os altos níveis de atividade nervosa simpática deflagrados pelas apnéias. Há prolongamento progressivo dos níveis elevados, particularmente de noradrenalina, durante o período de vigília

The Effects of Cilazapril on Left Ventricular Remodeling after Coronary Intervention in Patients with Ischemic Heart Failure

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.

Ventricular functions in children with human immunodeficiency virus infection after ACE-inhibitors.

Nine pediatric symptomatic patients infected with human immunodeficiency virus with elevated pulmonary arterial pressure (MPA pressure) and ejection fraction (EF); and with fractional shortening, (FS) mean velocity of circumferential fiber shortening (MVCfc) and left ventricular peak systolic wall stress (PS) were prospectively evaluated using 2-dimensional and M-mode serial echocardiography and Doppler cardiography after administration of an ACE inhibitor (Inhibace 0.025 mg/kg/D orally) for 12 weeks. The MPA pressure was not decreased, however the MVCfc and PS improved significantly (p < 0.05). Further, long term evaluation is required to determine its effect in preventing dilated cardiomyopathy and elevated mean pulmonary pressure.

Efecto del cilazapril, un inhibidor de la enzima de conversión, sobre la hipertrofia cardiovascular del paciente hipertenso / Effect of cilazapril, a converting enzyme inhibitor, on cardiovascular hypertrophy in the hypertensive patient

El aumento mantenido de las resistências vasculares periféricas es la alteración hemodinámica que caracteriza a la hipertensión arterial (HTA) establecida. Ello es el resultado de un incremento del tono vascular y los cambios estructurales que implican tanto la hipertrofia e hiperplasia de las fibras musculares lisas vasculares, la hipertrofia de las células cardíacas y un aumento de la síntesis de los componentes de la matriz extracelular. La angiotensina ll y la noradrenalina ejercen importantes efectos tróficos que aceleran la progresión de la hipertrofia cardiovascular siendo el aparato cardiovascular muy sensible a las acciones tróficas del sistema renina-angiotensina. La angiotensina ll induce la expresión de la cadena A del factor de crecimiento de origen plaquetario, del factor de crecimiento fibroblástico básico y del factor transformador B y además estimula la síntesis de colágeno tipo I y II y facilita la liberación de factores tróficos. Por lo tanto, el sistema renina-angiotensina juega un importante papel en la regulación del crecimiento y remodelación de los miocitos y de la matriz extracelular cardiovascular, que está mediado a través de receptores específicos, ya que puede inhibirse por antagonismo de los receptores ATl para la angiotensina II e IECA. El cilazapril es un IECA de larga duración que produce una reducción de la presión arterial y de la hipertrofia cardiovascular. El mecanismo responsable de esta acción es múltiple como su acción vasodilatadora, su capacidad para inhibir el tono simpático o para aumentar los niveles de kininas y particularmente su capacidad de inhibir el sistema renina-angiotensina cardíaco.

Estudo comparativo duplo-cego da eficácia e segurança do cilazapril comparadas à nifedipina "retard" no tratamento da hipertensäo arterial leve e moderada / Double-Blind Comparative Study of Efficacy and Safety of Cilazapril Compared to Nifedipine Retard in the Treatment of Mild and Moderate Hypertension

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

Monitorizaçäo ambulatorial da pressäo arterial com um novo inibidor da ECA--cilazapril / Ambulatory Blood Pressure Monitoring with Cilazapril. A New ACE Inhibitor

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.

A clinical study on the anti-Hypertensive effect of cilazapril in patients with mild to moderate essential hypertension

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.