OBJECTIVE: To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients. DESIGN AND METHODS: Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin ...

To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with ...

Mammals produce two isozymes of angiotensin-converting enzyme (ACE). Somatic ACE plays an important role in the control of blood pressure. The function of testis ACE, produced by male and germ cells, is not known. To examine the roles of these isozymes, we used targeted homologous recombination to introduce a modified ...

OBJECTIVE: To investigate the relationship between circulating angiotensin converting enzyme activity and arterial blood pressure in a population-based sample of 646 middle-aged subjects. RESULTS: After exclusion of subjects taking antihypertensive medication and those with electrocardiographic evidence of myocardial infarction, univariate analyses revealed that systolic blood pressure was significantly correlated with ...

OBJECTIVE: The aim of the present study was to investigate the functional regulation of the myocardial postreceptor adenylyl cyclase (AC) system in compensated left ventricular hypertrophy (LVH) and the effect of long-term angiotensin converting enzyme (ACE) inhibition. METHODS: Pressure overload LVH was induced in rats by supravalvular aortic banding for ...

The protective effects of ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y l]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied following long-term (for 8 months) oral administration. At a dose of 10 mg/kg/day, ME3221 suppressed the mortality and the hypertensive complications observed in control SHRSP: cerebral apoplexy (hemorrhage, and spongeform and malacia ...

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect ...

In congestive heart failure captopril modifies the left ventricular filling pattern mainly by unloading the heart. We investigated whether the structural characteristics of the left ventricle may influence the acute effects of captopril on this pattern in patients with untreated hypertensive (H group, 6 patients) or idiopathic (I group, 14 ...

This study assessed the usefulness of the oral captopril test in the prediction of renal impairment among elderly patients with congestive heart failure (CHF). Forty-seven patients aged > or = 65 years with CHF (EF < 40%) participated in a prospective nonrandomized series. Blood samples for plasma renin activity (PRA) ...

The effects of ACE inhibitors on the stenosed kidney in patients with unilateral arterial stenosis are not well characterised. While there are conflicting reports, some experimental and clinical evidence suggest that the stenosed kidney may undergo atrophy: secondary to effective blood pressure lowering and decreased perfusion pressure distally, or due ...

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, ...

A total of 35 patients in sinus rhythm and with mild-to-moderate congestive heart failure (CHF) (NYHA II-III) aged 53 (+/- 3) years were examined before therapy with angiotensin-converting enzyme (ACE) inhibitors. Of these patients, 16 were reexamined after therapy with ACE inhibitors for 17 +/- 3 days. The relation of ...

Angiotensin II may contribute to the altered structure and function of small arteries. We proposed that angiotensin I-converting enzyme (ACE) inhibitor treatment could induce a regression of vascular remodeling. A double-blind trial was performed comparing effects of the ACE inhibitor cilazapril with the beta-blocker atenolol on small arteries obtained from ...

The effects of calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors on blood pressure and the progression of renal dysfunction were compared in hypertensive patients with polycystic kidney disease (PKD). Twenty-six patients with PKD and hypertension who had been treated with other antihypertensive agents, such as diuretics, beta-blockers, ...

OBJECTIVE: To study the haemodynamic profile and tolerability of imidapril, a new long-acting ACE inhibitor, and to investigate the effect of inhibition of circulating ACE on blood pressure in patients with stable chronic heart failure. METHODS: Twenty-four patients with stable, chronic heart failure (New York Heart Association (NYHA) functional Class ...

OBJECTIVE: The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). METHODS: The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements ...

The pharmacological manipulation by vasodilators of peritoneal solutes and fluid kinetics was investigated. Rats were dialyzed for 240 minutes with 30 mL 4.25% glucose dialysate containing dextran 70. An angiotensin-converting enzyme inhibitor (captopril), three calcium channel blockers (nicardipine, diltiazem, and verapamil), and an +/-blocker (maxisylite) were administered intraperitoneally at various ...

1. The kallikrein-kinin system has a significant role in regulating arterial blood pressure. 2. Reduced formation of the kinin compontents may cause hypertensive diseases. This is because of the fact that this system is responsible for vasodilatation, reduction in total peripheral resistance, natriuresis, diuresis, increasing renal blood flow and releasing ...

OBJECTIVE: To provide clinical support that conversion from captopril to lisinopril at a daily oral dosage ratio of 5:1 maintains comparable therapeutic efficacy, and to estimate retrospectively cost savings because of conversion from captopril to lisinopril therapy at the study site and with the associated overall drug conversion program instituted ...

Arterial hypertension is associated with increased capillary permeability, a possible contributor to the vascular remodeling process which could be involved in certain pathological conditions arising from elevated blood pressure. This study evaluated the effects of various antihypertensive drugs on capillary permeability in the normal rat, using Evan's blue dye (EB) ...

There is recent interest in the possibility that angiotensin converting enzyme inhibitors (ACE inhibitors) may reduce the damage inflicted on the arterial wall by common cardiovascular risk factors such as hypertension, hyperlipidaemia and ageing. The efficacy of these drugs in blood pressure reduction is accepted, but whether there is an ...

OBJECTIVE: Daily exposure to air-jet stress (AJS) causes sustained elevations of blood pressure in borderline hypertensive rats (BHR). It is known that the renin-angiotensin system is activated during episodes of behavioral stress, and the purpose of this study was to assess the involvement of renin-angiotensin system in the development of ...

A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated ...

Distensibility and compliance are large artery properties, that may be important in cardiovascular disease. Distensibility is a determinant of the pulsatile stress on the vessel wall and is thought important in ageing and atherosclerotic disease. Compliance reflects the buffering capacity of the arteries and is a major determinant of the ...

Application of periarterial collars induced atheroma-like lesions in the carotid arteries of normocholesterolemic rabbits. Vessel segments taken from the mid-region of the collar (cuffed region) and control regions of the same artery were studied at 7 days after surgery. A group of placebo rabbits was provided ad libitum with regular ...

OBJECTIVES: Hypertension and hypercholesterolemia frequently coexist, necessitating concurrent treatments for both disorders. The present study aimed at evaluating the efficacy, the safety, and the toleration of captopril, an ACE inhibitor, hydrochlorothiazide, a diuretic, and pravastatin, a HMG-CoA reductase inhibitor co-administered in hypertensive patients in general practice. DESIGN: The patients were ...

BACKGROUND: An allelic variant of the ACE gene has been found to be linked to plasma angiotensin-converting enzyme (ACE) activity in humans and has been implicated in the etiology of some common cardiovascular disorders. Previously, we have shown significant genetic linkage of blood pressure to a region on rat chromosome ...

Combined neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) inhibition produces greater acute hemodynamic effects than either treatment alone. We investigated whether BMS-182657 (BMS), which bears inhibitory activities against both NEP and ACE, elicited similar enhanced effects. BMS inhibited NEP and ACE, in vitro (IC50 = 6 and 12 nM, respectively) ...

The past few decades have seen a remarkable development in the field of pharmacological therapy, one of the most notable examples being the treatment of arterial hypertension. Some of the early anti-hypertensive agents were relatively crude by today's standards, but gradually efficacy, tolerability, or both, of blood pressure-lowering (BP) drugs ...

Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day ...

Duration of action of an angiotensin converting enzyme (ACE) inhibitor is not solely related to its individual elimination half-life. It is also determined by its ACE inhibiting potency and affinity for ACE. Its degree of lipophilicity is also an important factor in determining tissue penetration. Any attempt to calculate the ...

The present study compares the hemodynamic effects and mechanisms of action of angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE) inhibitors, and renin inhibitors in the guinea pig, an animal with high similarity to primates in terms of in vitro and in vivo responses to several human renin inhibitors. Animals ...

Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class ...

The effects of growth hormone (GH) plus insulin-like growth factor-1 (IGF-1) were tested in an experimental model of cardiac failure treated with chronic angiotensin-converting enzyme (ACE) inhibition. Myocardial infarction was induced in rats by left coronary artery ligation. Two weeks after ligation, the animals received either captopril (2 g/L in ...

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects ...

OBJECTIVES: Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after clipping, and determined the cellular distribution ...

INTRODUCTION: Losartan potassium, an orally active, highly selective AT1 angiotensin II receptor inhibitor, effectively reduces blood pressure by direct receptor blockade, thereby lessening the likelihood of angiotensin converting enzyme (ACE) inhibitor-associated side effects such as dry cough or possibly angioedema. STUDY DESIGN: In this multinational, double-blind, randomized, parallel study, the ...

Depressed baroreflex sensitivity (BRS) after acute myocardial infarction (AMI) is considered an indication of decreased vagal and/or increased sympathetic tone. To determine the effect of angiotensin converting enzyme inhibitors (ACEI) on BRS after AMI we studied 27 patients with a first Q wave AMI, no signs of heart failure and ...

OBJECTIVE: To evaluate the antihypertensive efficacy of sinorphan, an orally active inhibitor of neutral endopeptidase EC 3.4.24.11. DESIGN: The ability of sinorphan (100 mg twice a day) to lower blood pressure was compared with that of the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg twice a day) using a ...

The effects of long-term treatment with a novel angiotensin I converting enzyme (ACE) inhibitor, trandolapril, on ACE activity and cardiac function in rats with chronic heart failure (CHF) were examined and compared with those of captopril and enalapril. Left coronary artery ligation of rats resulted in decreases in mean arterial ...

In this study delapril and captopril were compared in outpatients with congestive heart failure (CHF), New York Heart Association (NYHA) classes III and IV, in a double-blind study of efficacy and safety. Efficacy was evaluated by monitoring changes in the NYHA classification, exercise work, hemodynamic parameters, Kostuk's classification, and clinical ...

Delapril is a carboxy-alkyl-dipeptide mainly converted in animals and humans to an active diacid derivative (M-I), which in turn is converted to an active 5-hydroxy-indane diacid (M-III). In humans these metabolites are excreted in the urine. The presence of the indanyl-glycine moiety gives delapril a high lipophilicity, greater than several ...

Mean circulatory filling pressure (MCFP), whole body vascular compliance (C), and unstressed blood volume (USV) are important indexes of cardiovascular function in mammals, but they have not been measured in fish. In the present experiments, dorsal aortic (PDA) and sinus venosus (PSV) pressures were measured in unanesthetized trout before and ...

Chronic heart failure (CHF) impairs endothelium-dependent vasodilatation of large conductance arteries. We investigated whether a similar reduction also occurs in small arteries, and whether such a reduction can be prevented by the angiotensin converting enzyme inhibitor perindopril (P) in a rat model of CHF (left coronary artery ligation). After 1 ...

Spirapril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor prodrug which is converted to the active metabolite spiraprilat following oral administration, and which has been evaluated primarily for the treatment of hypertension. In dose-finding studies of patients with mild to severe hypertension, spirapril > or = 6 mg once daily ...

We have recently shown that the angiotensin I converting enzyme (ACE) gene is linked to NaCl-loaded blood pressure in the stroke-prone spontaneously hypertensive rat (SHRSP), and that high-NaCl loading selectively stimulates ACE in the aorta of SHRSP but not in normotensive Wistar-Kyoto (WKY) rats. We therefore investigated the relationship between ...

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal ...

Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, ...

To find out if there are one or more criteria to guide selection among the ACE inhibitors for the treatment of arterial hypertension, we have reviewed the principal pharmacokinetic and pharmacodynamic aspects of the more frequently used agents of this class of antihypertensive drugs. Among the pharmacokinetic aspects that we ...

The aim of this study was to assess the effects of Angiotensin Converting Enzyme (ACE) inhibition on cardiac systolic and diastolic parameters and left ventricular muscle mass in hypertensive patients. For this purpose 30 patients (22 female and eight male) with mild to moderate essential hypertension, aged 47 +/- 2 ...