Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alatriopril is a dual inhibitor of two cell surface metallopeptidases which play important roles in the regulation of arterial blood pressure and renal function: the angiotensin I converting enzyme (ACE) which catalyses transformation of angiotensin I to angiotensin II, and the neutral endopeptidase (NEP; EC 3.4.24.11; atriopeptidase), responsible for the degradation of the atrial natriuretic factor (ANF). The purpose of the present study was to evaluate the systemic and regional hemodynamic effects of alatrioprilat, the active part of alatriopril, in 6 anesthetized, closed-chest beagle dogs instrumented for the measurement of arterial pressure (aortic catheter), cardiac output (thermodilution), as well as femoral and renal artery flows (Doppler). Animal received alatrioprilat at the doses of 1 and 10 mg/kg (i.v. bolus). Hemodynamic parameters were measured at baseline, then 15, 30, 45 and 60 min after administration of each dose. In addition, plasma ANF and ACE activity were determined at baseline and 30 min after administration. At the dose of 1 mg/kg, alatrioprilat dit not induce marked hemodynamic effects, except a transient hypotension which appeared within the first 10 min after administration and lasted less than 10 min. Neither plasma ANF nor angiotensin converting enzyme activity were affected by this dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1993 Aug
PMID:[Systemic and regional hemodynamic effects of a new angiotensin converting enzyme and neutral endopeptidase mixed inhibitor, alatriopril, in the dog]. 812 43

The aim of this study was to determine the role of Doppler echocardiography in establishing the prognosis of Stages to 4 cardiac failure. The echocardiographic indices of left ventricular filling were correlated with catheter data and the 2 year out come of patients. The study population included 54 patients examined prospectively in the context of an evaluation of their cardiac failure. Two years after the initial examination, 19 patients were dead or transplanted. Of the remaining 35 patients, 18 were reevaluated at 6 months. Of the echocardiographic parameters, "hyper normal" mitral flow with a high E/A ration indicated poor prognosis; when E/A > 2, the one year survival was 50% and the 2 year survival 42%. There was overlap between the groups of dead or transplanted and surviving patients only when the E/A ratio was between 2 and 3. The patients with E/A < 2 were all alive without any major events at 2 years. All patients with E/A > 3 had a poor prognosis. The E/A ratio was closely correlated with pulmonary capillary pressure levels (p < 0.001, r = 0.55) and lees closely with cardiac index (p < 0.05, r = 0.4) and radionuclide ejection fraction (p < 0.05, r = 0.28). After 6 months' vasodilator treatment with an angiotensin converting enzyme inhibitor (captopril) the E/A ratio decreased significantly from 1.85 +/- 0.78 to 1.0 0.55 (p < 0.02). A "hyper-normal" mitral flow is related to many factors, including high left ventricular filling pressures, mitral regurgitation and reduced left ventricular compliance. This appearance of mitral flow is a poor prognosis factor in severe cardiac failure.
Arch Mal Coeur Vaiss 1993 Sep
PMID:[Doppler echocardiographic evaluation of mitral flow velocity and prognosis of cardiac insufficiency]. 812 51

Chronic cardiac failure is an important problem of public health because of its prevalence and high mortality. A better understanding of its physiopathology and the detrimental effect of neurohormonal activation that it induces were the reasons for the utilisation of angiotensin converting enzyme inhibitors leading to symptomatic improvement and also a reduction in the mortality of severe cardiac failure, as demonstrated in the CONSENSUS study published 5 years ago. Since then, cardiologists have presented ACE inhibitors in all stages of cardiac failure, but is this attitude justified? More explicitly, are ACE inhibitors the drugs of choice in cardiac failure? Before acknowledging this label "drug of choice" in the treatment of chronic cardiac failure, ACE inhibitors should fulfill certain reference criteria proposed by Packer for the treatment of this condition: rapid relief of symptoms; reduced mortality; modification of the natural history of the condition; efficacious and well tolerated. The effects of ACE inhibitors are analysed critically taking into account the results of large scale therapeutic trials (SOLVD, V-HeFT II, CONSENSUS II, SAVE), which have been reported recently? The reported results confirm clinical impressions: ACE inhibitors are the drugs of choice of all stages of chronic cardiac failure but in association with diuretic and digitalis therapy.
Arch Mal Coeur Vaiss 1993 Feb
PMID:[Should cardiac insufficiency be first treated by angiotensin converting enzyme inhibitors?]. 821 88

The effects of an angiotensin converting enzyme (ACE) inhibitor on the intrinsic contractility of the myocardium in cardiac failure have not been studied intensively. The authors studied inotropism, lusitropism and economy of contraction in vitro on left ventricular papillary muscle preparations of cardiomyopathic Syrian hamsters (CSH) treated preventively with perindropil, i.e. before overt signs of cardiac failure. The CSH of the dilated Bio 53.58 strain aged 1 month were treated with perindropil 1 mg/Kg/day for 5 months (PE, N = 11) or with placebo (PL, N = 11) and control hamsters of the F1B strain received placebo (C, N = 7). Compared with C, PL had a significant reduction of the maximal velocity of contraction Vmax (p < 0.01) and of total isometric tension (TF/mm2), p < 0.05, and a reduction of the G curve of the hyperbolic Hill Force-Velocity relationship (p < 0.01). The G value is usually greater in models with improved economy of contraction. When compared with PL, PE showed a 68% inhibition of the plasma activity of ACE, a better Vmax (p < 0.05) but an unchanged TF/mm2. The G value was less depressed than that of C (p < 0.05). The velocity of isotonic relaxation (maxVL) and the negative peak of the derivative of the isometric force (-dF/dt max) were significantly lower in the PL than in the C group but these lusitropic abnormalities remained coordinated with those of the contraction phase, indicating the absence of an intrinsic effect on relaxation in cardiomyopathy. Perindopril prevented the reduction of maxVL but not that of -dF/dt max.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1993 Feb
PMID:[Protective effects of perindopril in an experimental model of cardiomyopathy]. 821 90

In adult acquired hypogammaglobulinaemia multi focal granulomas have often been described and have regularly led to the hypothesis of an association with sarcoidosis. We present a case of this type in a man aged 29 who was a smoker with a hypoglobulinaemia involving IgG, IgA and IgM and which was discovered following pneumococcal pneumonias. He presented with a significant hepatosplenomegaly and absent cutaneous reactions to T dependent antigens with an elevated ACE activity. Histological examination of the splenectomy specimen and of the liver biopsy showed an infiltration by epithelioid follicles and confluent giant cells without necrosis. The pulmonary studies showed a normal chest radiograph but the bronchial biopsy again found a granulomatous infiltration. The broncho-alveolar lavage was cytologically normal and a very slight and paradoxical reduction of the alveolar immunoglobulins was noted implying either an active intra-alveolar concentration of immunoglobulins or a local synthesis. In the light of the few reported cases it seems that the diagnosis of sarcoidosis should be dismissed here in favour of multi focal granulomatosis with hypogammaglobulinaemia. In hypogammaglobulinaemia there is no clinical or biological method (IDR tuberculin, ACE, Kveim, histology) to confirm a superadded diagnosis of sarcoidosis.
Rev Mal Respir 1993
PMID:[Acquired hypogammaglobulinemia and multifocal granulomatosis]. 825 39

The authors studied the responses of the main systems of sympathetic and hormonal regulation in valvular aortic stenosis, a special model of dissociation between arterial pressure and left ventricular function. The series comprised 14 patients with an average age of 70 +/- 9 years without diuretic therapy presenting with pure calcific aortic stenosis without other valvular or coronary disease. All were in sinus rhythm; 5 were taking an angiotensin converting enzyme inhibitor. Plasma concentrations of endothelin 1, atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, plasma renin activity (PRA), angiotensin II and aldosterone were measured in resting, fasting patients, by blood samplings from a peripheral vein immediately before cardiac catheterisation. The results were compared with the severity of the aortic stenosis (aortic valve area greater or less than 0.7 cm2), the ratio of left ventricular work/myocardial mass (greater or less than 0.6) and treatment (with or without ACE inhibitors). Catecholamine levels were much higher in severe aortic stenosis (noradrenaline: 579 +/- 66 pg/ml when valve surface area > 0.7 cm2 versus 900 +/- 92 pg/ml when valve surface area < 0.7 cm2; p < 0.01). Endothelin -1 and AVP concentrations were normal. Whereas PRA was normal, aldosterone levels were increased in patients without treatment by ACE inhibitors. This treatment did not, however, normalise the noradrenaline levels. The increase in ANF concentration was large when left ventricular work decreased with respect to myocardial mass (190.8 +/- 42.3 pg/ml if W/M was decreased versus 82.7 +/- 15.4 pg/ml when W/M was normal): this could be related to the degree of left ventricular hypertrophy.
Arch Mal Coeur Vaiss 1993 Jul
PMID:[Neurohormonal profile in aortic valve stenosis]. 829 34

The aim of the study was to assess the effects of a one-month treatment period with the ACE inhibitor trandolapril (0.3 mg/kg/day) on the endothelial reactivity in epicardial right coronary arteries (CA) of 26-30 week-old SHRs. For this purpose, segments of CA were mounted in an arteriograph where wall thickness and internal diameter (ID) were continuously monitored while intraluminal pressure (IP) was controlled. In the absence of flow and under an IP of 30 mmHg, IDs were not significantly different in control compared to those of treated SHR arteries (microns, 250 +/- 8 vs 240 +/- 7). In preconstricted preparations (5HT, 10 microns extraluminally) C/E curves were constructed by adding acetylcholine (AC, 0.01-10 microM) or bradykinin (BK, 0.01-10 microM) in the bath. On the other hand, the effect of a stepwise increase in intraluminal flow (50-450 microliters/min; IP = 30 mmHg) of perfusion solution was observed. The effects of subsequent additions of sodium nitroprusside (SNP) were assessed. Maximal relaxations were expressed as percent of maximal contractions. Results were as follows: [table: see text] These results show that the endothelium-dependent relaxation induced by AC and BK were significantly increased in coronary arteries of treated compared to control SHRs whereas the flow-induced relaxation seemed to remain unaffected in our experimental conditions. From these data, it can be concluded that a short period of ACE inhibition in SHRs is able to improve the endothelium-dependent vasodilation induced by agonists in the coronary arterial bed.
Arch Mal Coeur Vaiss 1995 Aug
PMID:[Effects of short-term treatment with trandolapril on vasodilatator responses mediated by receptors or on blood flow in the coronary arteries in SHR]. 857 51

The aim of this study was to document changes in drug prescription after myocardial infarction. One hundred and seventy four men with typical myocardial infarction recensed by the Toulouse MONICA centre between 1989 and 1990 were followed up for 4.5 years. A copy of their drug prescription was obtained during the acute phase of infarction, at the time of discharge from hospital or clinic, after 6 months, and finally, after 4.5 years after infarction. During the acute phase, the majority of patients received nitrate derivatives, platelet antiaggregants, calcium antagonists, betablockers and antiarrhythmics. Between hospital discharge and the sixth month, the prescription of lipid lowering drugs quadrupled (from 8 to 33%; p < 0.00001) and those of platelet anti-aggregants decreased (from 82 to 70%; p < 0.01). The prescriptions of other drugs remained relatively stable. Between the 6th month and the 4th year of follow-up the only prescription to increase significantly was that of ACE inhibitors (from 14 to 23%; p < 0.03). The other prescriptions were maintained: platelet anti-aggregants (70% at 6 months vs 75% at 4.5 years), nitrate derivatives (59 vs 51%), betablockers (51 vs 52%), calcium antagonists (51 vs 48%), lipid lowering drugs (33 vs 42%), diuretics (3 vs 6%) and inotropic agents (2 vs 2%). Overall analysis showed an increase in the prescriptions of lipid-lowering agents (p < 0.00001) and ACE inhibitors (p < 0.002). On the other hand, the prescriptions of calcium antagonists and nitrate derivatives tended to decrease. These results show that the treatment of patients with coronary artery disease is based on drugs of proven efficacy, reflecting the impact of large scale therapeutic trials on everyday medical practice.
Arch Mal Coeur Vaiss 1996 Jan
PMID:[Long-term effects of prescription drugs in 174 patients treated for myocardial infarction, followed up from 4 to 5 years (the DEVENIR study)]. 867 36

Congestive cardiac failure is characterised by redistribution of blood flow to the brain and the heart at the expense of the kidneys. The prognosis of this condition at its most advanced stage (stage IV) is poor with a mortality of about 50% at 5 years. The reduction of renal perfusion will lead to stimulation of all vasoconstrictor and anti-natiuretic mechanisms, and to a parallel activation of vasodilator and natiuretic systems. There is, therefore, a clear conflict of interest between the heart, which attempts to preserve its perfusion and function, and the kidneys which aggravate the haemodynamic disturbances by salt and water overload and the risk of arrhythmias due to hypokalaemia and hypomagnesaemia. The diuretics and ACE inhibitors are essential therapeutic classes for the treatment of congestive cardiac failure. The prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, potassium and magnesium concentrations, is based on an initial low dose prescription, the detection and correction of risk factors and strict clinical and biological surveillance. In order to avoid the risks of hyperkalaemia during the association of ACE inhibitor and diuretic therapy with a potassium sparing agent, the initial dose of these two drugs should be as low as possible.
Arch Mal Coeur Vaiss 1996 Jun
PMID:[Treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics]. 876 Jun 60

Ischaemic heart disease is a perfect example of variability. The official mortality statistics in Europe show a gradient from 1 to 5. France is a zone at low risk even if deaths of undetermined causes are taken into account. This gradient is confirmed by the data from the Registries of the MONICA project. In France, the official mortality figures show a decrease of 28% in coronary mortality between 1985 and 1991 in men, throughout France. The differences in incidence of myocardial infarction between Lille and Toulouse in the MONICA project are not important but the differences in mortality are worrying. Between 1985 and 1991, the three registries show a 7% decrease in mortality (p < 0.001) and a 25% decrease in recurrences (p < 0.001) with an increase in primary infarcts of 8.3% (p < 0.05). There has been an increase in the prescription of betablockers, thrombolytics, ACE inhibitors and aspirin during the acute phase and at discharge form hospital. French cardiologists have followed the recommendations of the large scale clinical trials published during this period. The improved hospital mortality corresponds to the beneficial results reported in trials with aspirin, betablockers, ACE inhibitors and thrombolytics.
Arch Mal Coeur Vaiss 1996 Aug
PMID:[Epidemiology according to the European and French scales of myocardial infarction. Data of the MONICA project]. 894 13


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