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 140/90 mmHg. 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% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (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.

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.

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.

[Transient ischemic attacks in a patient with superior vena cava obstruction: case report]. / Ataques isquêmicos transitórios em paciente com síndrome da veia cava superior. Relato de caso.

The superior vena cava obstruction is a relatively rare condition. We report the case of a 42 year old man suffering of hypertension for about fifteen years. He reported a cervical and thoracic pain for one year, that was related to a 95% of occlusion on the right coronary artery. An angioplasty has been done but the patient still related the thoracic pain. Afterwards the patient had recurrent episodes of right hemiplegia and hypertensive emergencies that have been treated with anti-hypertensive agents. A venous disease was suspected because of cyanosis in the face especially when episodes of transient ischemic attacks occurred. A venography showed obstruction of the right jugular vein near the junction with the superior vena cava. In conclusion, it was not possible to define with certainty the relationship between the two pathologies presented by the patient, even so, we call attention to the improvement of the neurological symptoms after the control of superior vena cava obstruction with the treatment.

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

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 resistÛncias 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. (AU)

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.

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

The sustained increase in peripheral vascular resistance is the hemodynamic alteration characteristic of the established adult hypertension. This is the result of a vascular tone increase and/or structural changes which imply hypertrophy as well as hyperplasia of the vascular smooth muscle fibers, hypertrophy of the cardiac cells and an increase in the constituent synthesis of the extracellular matrix. Angiotensin II and noradrenalin exert major trophic effects which accelerate the progression of cardiovascular hypertrophy being the cardiovascular system very sensitive to the trophic actions of renin-angiotensin. Angiotensin II induces the expression of the A-chain of the growth factor of platelet origin, of the baseline fibroblastic growth factor and of the B-transformer factor and, moreover, stimulates type I and type III collagen synthesis and favors trophic factors release. Therefore, the renin-angiotensin system plays an important role in growth regulation and myocyte remodelation and in the cardiovascular extracellular matrix which is mediated through specific receptors, since it can be inhibited by ATI receptor antagonists for angiotensin II and ACE. Cilazapril is an ACE long duration agent which produces a reduction of both blood pressure and cardiovascular hypertrophy. This is a multiple action mechanism exerting a vasodilator action, inhibiting the sympathetic tone or increasing kinine levels and inhibiting the cardiac and vascular renin-angiotensin system.

[Comparative and double-blind study of the efficacy and safety of cilazapril compared to nifedipine retard in the treatment of mild and moderate arterial hypertension]. / Estudo comparativo duplo-cego da eficácia e segurança do cilazapril comparadas à nifedipina "retard" no tratamento da hipertensão arterial leve e moderada.

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% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. CONCLUSION: Cilazapril 2.5 to 25mg normalized BP in 58% 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.

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

[Ambulatory monitoring of blood pressure with a new ACE inhibitor--cilazapril]. / Monitorização ambulatorial da pressão arterial com um novo inibidor da ECA--cilazapril.

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%). 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.

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.

[Cilazapril, a new ACE inhibitor, in severe arterial hypertension]. / Cilazapril, un nuevo inhibidor de ECA, en la hipertensión arterial severa.

We assessed the efficacy and safety of cilazapril, alone or in combination with hydrochlorothiazide. It was an open trial, that included 14 patients with or more 114 mmHg of diastolic arterial tension. On the first stage of 25 days, the arterial tension was normalized in 5 patients with 10 mg of cilazapril and 7 patients when hydrochlorothiazide was added, 2 patients did not respond. On the second stage of 52 weeks, of the 12 patients whose diastolic arterial tension was normalized, 2 patients remained with normal arterial tension with cilazapril, 5 when hydrochlorothiazide was added and the rest 5 patients did not respond. No undesirable side effects were detected, nor abnormalities in the laboratory tests. The long-term benefit obtained on 50% of patients make evident the usefulness of cilazapril in severe arterial hypertension. Its administration once a day and the absence of side effects increase the interest of its use.

Effect of cilazapril in hypertensive patients with renal impairment.

The aim of the study was to evaluate the clinical and renal hemodynamic effects of cilazapril in 10 hypertensive patients with moderate-to-severe chronic renal failure (creatinine clearance 14-50 ml/min). After 2 weeks of placebo, cilazapril 0.5 mg/day was given, and the dose was increased up to 5 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Once a normal SDBP value was achieved, the patients remained on the given dose regimen for 6 months. After this period SDBP decreased from 107 +/- 2 to 95 +/- 2 mm Hg (p less than 0.001). At the end of treatment, glomerular filtration rate (GFR) remained unchanged in five patients, improved in four patients, and slightly decreased in one patient, the slope from baseline being 0.137 and the variation of GFR per unit of GFR at baseline being between -0.20 and 0.47. Likewise, effective renal plasma flow increased not significantly, showing considerable variability. Urinary protein excretion was reduced significantly from 2.51 +/- 0.75 to 0.51 +/- 0.10 g/L (p less than 0.05), suggesting that converting enzyme inhibition may exert a renal protective effect. In conclusion, it appears that cilazapril does not induce functional damage in the kidney of predialysis hypertensives.

Effects of ACE inhibition on renal haemodynamics in essential hypertension and hypertension associated with chronic renal failure.

Angiotensin II has many actions in the kidney, including regulation and distribution of renal circulation and glomerular filtration, as well as effects on mesangial contraction and on the filtration coefficient. The reduction in circulating and intrarenal angiotensin II by angiotensin converting enzyme (ACE) inhibitors in essential hypertension is associated with a significant increase in renal blood flow and a decrease in filtration fraction, without changes in glomerular filtration rate. In addition, administration of ACE inhibitors can reduce proximal sodium reabsorption via changes in peritubular hydrostatic and oncotic forces resulting from the fall in postglomerular capillary resistance. In severe hypertension the state of the renal vasculature does not allow ACE inhibition to induce similar haemodynamic changes and, therefore, it cannot contribute to renal sodium handling that requires the recruitment of alternate mechanisms. In spite of this, ACE inhibitors may exert a protective effect on the renal function of patients with severe hypertension as well as in those with renal impairment, by lowering systemic and, probably, intraglomerular pressure, reducing proteinuria and slowing the progression of renal failure.

Long-term evaluation of cilazapril in severe hypertension. Assessment of left ventricular and renal function.

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide was assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echo-cardiography. Sitting systolic blood pressure was reduced from 175.8 +/- 2.0 to 143.3 +/- 3.0 mmHg within 25 days of therapy (p less than 0.0001); sitting diastolic blood pressure decreased in the same period from 117.0 +/- 1.0 to 87.8 +/- 2.0 mmHg (p less than 0.0001), whereas heart rate remained unchanged. In 19 patients treated for an average of 48 weeks the therapeutic response was maintained during the long-term period. The mean effective dose was cilazapril 10 mg plus hydrochlorothiazide 12.5 to 25 mg in 90 percent of the patients. Left ventricular mass decreased from 357 +/- 17 to 314 +/- 22 g (nine patients; p less than 0.005) and a correlation (Spearman r = 0.57, p less than 0.01) was found between left ventricular mass and sitting systolic blood pressure before and during treatment. Deceleration half time of peak early diastolic inflow velocity decreased significantly from 128 +/- 9 to 108 +/- 7 msec (p less than 0.05). Glomerular filtration rate and renal blood flow remained within normal limits, whereas renal vascular resistance decreased from 0.16 +/- 0.0 to 0.10 +/- 0.0 resistance units (10 patients; p less than 0.01). Cilazapril in combination with hydrochlorothiazide was effective in the treatment of severe hypertension. Left ventricular hypertrophy regression influenced favorably left ventricular diastolic function in some patients, whereas renal hemodynamics were generally not affected by the therapy.

Antihypertensive, enzymatic, and hormonal activity of cilazapril, a new angiotensin-converting enzyme inhibitor in patients with mild to moderate essential hypertension.

The antihypertensive activity of cilazapril, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor was evaluated in 20 outpatients (13 women, 7 men; mean age, 49 +/- 2.4 years) with mild to moderate essential hypertension, by means of an open dose-finding study of 10 weeks' duration. Cilazapril, 0.5 mg/day, was given, and the dose increased up to 10 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Blood pressure measurements were carried out every 2 weeks before and 2 h after dosing. Predose and 2-h postdose measurements of plasma renin activity (PRA), angiotensin II (AII), plasma aldosterone (PA), and enzyme converting activity (ECA) were performed on the 1st day of active treatment and after 2 weeks of therapy. The SDBP decreased from 107.6 +/- 2 to 97.2 +/- 3 mm Hg 2 h after the initial dose (p less than 0.01). At the same time, ECA was inhibited 84.2 +/- 5% (p less than 0.01), AII decreased from 21.2 +/- 3 to 13.6 +/- 2 pg/ml (p less than 0.05), and PA from 208 +/- 29 to 119 +/- 14 pg/ml (p less than 0.01). After 2 weeks of therapy, ECA remained markedly reduced, by 68 +/- 6%, 24 h after the preceding cilazapril dose (p less than 0.01). The mean SDBP decreased from baseline to the end of treatment by 14.6 +/- 3 mm Hg (p less than 0.01). Cilazapril seems to be an effective antihypertensive drug which exerts potent and long-lasting ACE inhibition.