Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The 24-h profile of blood pressure (BP) was studied in 28 patients (21 males and 7 females) with congenital heart failure (CHF) of NYHA class II-III (ejection fraction < 45%). The patients were 46 to 76 years of age and had postinfarction cardiosclerosis. They had not received ACE inhibitors before. Two groups were formed basing on the presence of hypertension. Perindopril was administered in a single daily dose of 2 mg or higher if demanded to reduce symptoms of CHF and/or to normalize BP. The treatment continued for 3 months. The 24-h BP profile was assessed using portable device SpaceLabs 90207 (USA). In CHF patients with hypertension perindopril significantly lowered mean 24-h, day and night BP and its loads, reestablished two-phase circadian rhythm of AP and corrected BP variability. In CHF patients free of hypertension significant changes of the profile were not registered. It is evident that unwanted changes in the BP 24-h profile due to perindopril were absent in CHF normotensives.
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PMID:[Change of circadian pattern of arterial pressure in patients with congestive heart failure treated with perindopril, an inhibitor of angiotensin-converting enzyme (ACE)]. 950 33

The sympathetic nervous system, coronary artery disease and myocardial ischaemia are related in different ways. First, the sympathetic system may be involved in the process of atherosclerosis through platelet activation and subsequent platelet-derived growth factor formation and by inducing mechanical injury to the vascular wall as a result of increased blood pressure and increased flow velocity. Secondly, sympathetic control of coronary vasomotor tone, which under normal conditions is not important, becomes functionally significant once coronary artery disease endothelial dysfunction has occurred. Under these circumstances, increased sympathetic adrenergic tone may lead to coronary vasoconstriction and, as myocardial oxygen demand increases concomitantly, myocardial ischaemia may ensue. Alternatively, myocardial ischaemia activates several neurohormonal systems, such as the sympathetic and, during more severe ischaemia, the circulating renin-angiotensin system. This leads to systemic and, possibly, coronary vasoconstriction and thus to further myocardial ischaemia. Prolonged myocardial ischaemia results in progressive norepinephrine release from the heart, reaching extracellular levels as high as 100-1000 x plasma concentrations. As cardiac beta-receptor density rises simultaneously, sympathetically-induced irreversible myocardial damage may occur, although through concomitantly increased beta-receptor kinase activity the beta-receptor may become functionally inactive. To counteract the detrimental effects of enhanced sympathetic activation on the heart, beta-blockade appears to be the proper choice. However, acute beta-blockade may lead to more profound ischaemia-induced neurohormonal activation and hence to vascular constriction through unoccupied alpha-receptors. In contrast, under ischaemic conditions and with concomitant beta-blockade, acute alpha-blockade does improve subendocardial flow and reduces myocardial ischaemia. A novel approach to anti-ischaemic therapy, which relates to modulating ischaemia-induced sympathetic activation, is through ACE inhibition. ACE inhibitors affect myocardial ischaemia by reducing neurohormonal activation and related systemic and coronary vasoconstriction. These acute effects may become more important over time, as coronary endothelial function improves following long-term ACE inhibition. A large multicentre controlled trial comparing ACE inhibition with placebo in patients with coronary artery disease, the EUROPA (EUopean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease), which is currently underway, addresses the issue of whether ACE inhibition does in fact offer a novel approach in myocardial ischaemia.
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PMID:The sympathetic nervous system and ischaemic heart disease. 965 38

During ischaemia, both the circulating renin-angiotensin system and the local angiontensin converting enzyme are activated. The circulating renin-angiotensin system has a short-term role in the regulation of the cardiovascular system. Its aim is to restore blood pressure and cardiac homeostasis. Activation of the local system causes long-term regulation of cardiovascular homeostasis via sustained activation of local angiotensin and the gradation of bradykinin. This results in the secondary permanent structural changes that underline many aspects of coronary artery disease. Recently it has been shown that ACE inhibition is useful in the early and late phase of myocardial infarction. ACE inhibitors have been shown to reduce in vitro vascular hypertrophy and attenuate arteriolosclerosis and to maintain endothelial function. Interestingly, unexpected data from trials on heart failure have shown that patients receiving ACE inhibitors have a reduced incidence of infarction, hospitalization for cardiovascular disease and the need for coronary artery bypass surgery or angioplasty. As a consequence, several trials have been designed to assess the effect of ACE inhibition on the progression of coronary artery disease, as well as on its morbidity and mortality. The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) is one of these. This article summarised a number of independent and complementary mechanisms and points to the role played by ACE and ACE inhibition in coronary artery disease. In particular it considers the possibility that ACE inhibition improves endothelial function, exerts anti-atherogenic and anti-proliferation activity and modulates sympathetic activity.
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PMID:Effect of ACE inhibition on myocardial ischaemia. 979 38

The combination of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) inhibition is a candidate therapy for hypertension and cardiac failure. Given that NEP and ACE metabolize angiotensin (Ang) and bradykinin (BK) peptides, we investigated the effects of NEP inhibition and combined NEP and ACE inhibition on the levels of these peptides. We administered the NEP inhibitor ecadotril (0, 0.1, 1, 10, 100 mg/kg per day), either alone or together with the ACE inhibitor perindopril (0.2 mg/kg per day), to rats by 12 hourly gavage for 7 days. Ecadotril produced diuresis, natriuresis, increased urine cyclic guanosine monophosphate and BK-(1-9) levels, increased Ang II and Ang I levels in plasma, and increased Ang I levels in heart. Perindopril reduced Ang II levels in kidney, and increased BK-(1-9) levels in blood, kidney and aorta. Combined NEP/ACE inhibition produced the summation of these effects of separate NEP and ACE inhibition. In addition, perindopril potentiated the ecadotril-mediated diuresis, natriuresis and decrease in urine BK-(1-7)/BK-(1-9) ratio, which is an index of BK-(1-9) metabolism. Moreover, combined NEP/ACE inhibition increased Ang II levels in plasma and lung. These data indicate that summation of the effects of separate NEP and ACE inhibition provides the basis for the therapeutic efficacy of their combination. Whereas potentiation by perindopril of the diuretic and natriuretic effects of ecadotril may contribute to the therapeutic effects, increased Ang II levels in plasma and lung may compromise the therapeutic effects of combined NEP/ACE inhibition.
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PMID:Effects of neutral endopeptidase inhibition and combined angiotensin converting enzyme and neutral endopeptidase inhibition on angiotensin and bradykinin peptides in rats. 980 82

Combined inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) is a candidate therapy for hypertension and cardiac failure. Given that NEP and ACE metabolize angiotensin (Ang) and bradykinin (BK) peptides, we investigated the effects of NEP inhibition and combined NEP and ACE inhibition on Ang and BK levels in rats with myocardial infarction. We administered the NEP inhibitor ecadotril (0, 0.1, 1, 10, and 100 mg/kg/day), either alone or together with the ACE inhibitor perindopril (0.2 mg/kg/day) by 12-hourly gavage from day 2 to 28 after infarction. Ecadotril increased urine cyclic GMP and BK-(1-9) excretion. Perindopril potentiated the effect of ecadotril on urine cyclic GMP excretion. Neither perindopril nor ecadotril reduced cardiac hypertrophy when administered separately, whereas the combination of perindopril and 10 or 100 mg/kg/day ecadotril reduced heart weight/body weight ratio by 10%. Administration of ecadotril to perindopril-treated rats decreased plasma Ang-(1-7) levels, increased cardiac BK-(1-9) levels, and increased Ang II levels in plasma, kidney, aorta, and lung. These data demonstrate interactions between the effects of NEP and ACE inhibition on remodeling of the infarcted heart and on Ang and BK peptide levels. Whereas increased cardiac BK-(1-9) levels may contribute to the reduction of cardiac hypertrophy, the reduction in plasma Ang-(1-7) levels and increase in Ang II levels in plasma and tissues may compromise the therapeutic effects of combined NEP/ACE inhibition.
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PMID:Interaction between neutral endopeptidase and angiotensin converting enzyme inhibition in rats with myocardial infarction: effects on cardiac hypertrophy and angiotensin and bradykinin peptide levels. 1008 17

Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.
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PMID:First-dose response to angiotensin-converting enzyme inhibition in congestive cardiac failure: a Malaysian experience. 1034 62

Aldosterone biosynthesis in kidney has been proved by means of kidney perfusion in vitro, high performance liquid chromatography, radioimmunoassay and TR-PCR, indicating that aldosterone biosynthesis is possible in tissues other than adrenal. Bilateral nephrectomy was carried out in male Wistar rats and the plasma renin activity would disappear after 30 hours. However, RT-PCR showed that the vasculature in the nephrectomized rats was still able to express renin mRNA. It means that the vasculature is different from the heart which depends on taking up renin from the circulation, while the vasculature takes renin produced locally in its own tissue to initiate the renin-angiotensin-aldosterone system. Perindopril, an angiotensin converting enzyme inhibitor (ACEI), inhibits not only the production of angiotensin II, but also the synthesis of aldosterone in the vasculature. ACEI reversion of vascular remodeling is probably related with its inhibition of aldosterone synthesis in the vasculature.
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PMID:[An experimental study on tissue renin-angiotensin-aldosterone system]. 1043 67

The present study was designed to evaluate trough-to-peak ratio (T/P) of ACE inhibitors in spontaneously hypertensive rats (SHR) by a continuous monitoring of ambulatory blood pressure for 24 hours with a biotelemetric system. Blood pressure was recorded uninterruptedly with a battery-operated transmitter connected to a sensor catheter. Perindopril (3 mg/kg), trandolapril (1 mg/kg), quinapril (10 mg/kg) and enalapril (6 mg/kg) were given once a day for 7 days. On the first day of the treatment these ACE inhibitors equally decreased blood pressure by 20 mmHg at each peak. The peak and trough blood pressure decreased steadily until day 4, and then they were constant until the end of experiment (day 7). T/P for each inhibitor also increased until day 4, and the ratios in systolic blood pressure at the end of experiments (day 7) were as follows, perindopril: 0.63, trandolapril: 0.62, quinapril: 0.41, enalapril: 0.27. The T/P of perindopril was significantly higher than that of enalapril. The results of the present studies testing four ACE inhibitors are well consistent with those in clinical trials. Thus, the measurement of T/P in SHR would provide a meaningful information for the evaluation of antihypertensive agents like ACE inhibitors.
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PMID:Evaluation of high through-to-peak ratio of perindopril in SHR. 1051 38

ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run-in, double blind, crossover study, using 24-hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4-8 mg and enalapril 10-20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo-corrected peak (P) reduction of blood pressure (BP) of -6.4 +/- 1.3 mmHg vs its placebo-corrected trough (T) of -5.2 +/- 1.7 mmHg. Enalapril had a reduction in DBP of -8.5 +/- 1.3 mmHg (P) and -5.7 +/- 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of -7.5 +/- 1.6 mmHg (P) vs -7.3 +/- 2.2 mmHg (T) compared to enalapril with -10.8 +/- 1.6 mmHg (P) vs -8.3 +/- 2.3 mmHg (T). Placebo-corrected trough-to-peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24-hour mean BP, area under the curve or post-dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24-hour cover for the patient without excessive peak effect or poor trough effect.
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PMID:Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring. 1056 64

1. Hypoxic pulmonary hypertension in rats (10% O2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2. Perindopril (30 mg kg-1 d-1) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3. Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries <50 microm o.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30 - 100 and 101 - 500 microm o.d.). Perindopril 10 and 30 mg kg-1 d-1 attenuated remodelling in vessels < or = 100 microm (lungs and histology), 30 mg kg-1 d-1 was effective in vessels 101 - 500 microm but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg-1 d-1 was without effect. 4. Perindopril (30 mg kg-1 d-1) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5. We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.
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PMID:Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function. 1060 19


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