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)

We studied 14 patients who had exercise-induced ventricular arrhythmias after a previous Q-wave myocardial infarction. All had symptomatic mild heart failure in New York Heart Association class II and a maximal oxygen consumption between 16 and 20 ml/kg/min. They were treated with the angiotensin converting enzyme inhibitor benazepril (20 mg) and hydrochlorothiazide (50 mg) for 3 months in a double-blind randomized cross-over study. Benazepril improved the maximal oxygen uptake by 15% and exercise time by 18%. Hydrochlorothiazide slightly increased exercise time (5%) and the respiratory exchange ratio but not oxygen consumption. The arrhythmias were nonsustained and reproducible in two baseline recordings. Compared with baseline, benazepril reduced the mean number (3.5 +/- 2.5) (+/- SD) of episodes of ventricular tachycardia by 66%, and total (47.4 +/- 40.9) and paired (5.2 +/- 4.5) premature ventricular contractions by 61% and 62%, respectively. Hydrochlorothiazide did not reduce the number of arrhythmias. Thus an improved cardiac function induced by benazepril is associated with a reduction in exercise-induced ventricular arrhythmias in patients with symptomatic mild heart failure after infarction.
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PMID:Reduction of exercise-induced ventricular arrhythmias in mild symptomatic heart failure by benazepril. 767 69

Recent studies have shown that, not only in hypertensive animals but even in normotensive rats, dietary salt (sodium chloride) produces a dose-related increase in the left ventricular and renal mass. In the present study the effects of the angiotensin converting enzyme inhibitor (ACEI) enalapril and the thiazide-type diuretic, hydrochlorothiazide, on the development of the salt-induced left ventricular and kidney hypertrophy were examined in normotensive Wistar-Kyoto and Wistar rats. A high intake of sodium chloride (6% of the dry weight of the chow to mimic the level found in many human food items) during eight weeks produced a marked increase in the mass of the left ventricle and the kidneys in both rat strains with little or no effect on blood pressure. The cardiac hypertrophy correlated strongly with the renal hypertrophy. These salt-induced changes in the heart and in the kidneys were completely blocked by hydrochlorothiazide, while enalapril was devoid of any significant effects during the high-salt diet. However, during a low-salt diet enalapril, but not hydrochlorothiazide, effectively lowered the blood pressure and decreased the left ventricular mass of the normotensive rats. There was a 3- to 4-fold increase in the urinary excretion of calcium during the high intake of sodium chloride. Hydrochlorothiazide decreased the urinary excretion of calcium even during the low salt diet, and it completely blocked the salt-induced hypercalciuria. Enalapril had no significant effect on the urinary calcium excretion. During the low-salt diet hydrochlorothiazide increased the calcium and decreased the potassium concentration in the heart while enalapril increased the phosphorus concentration. In conclusion, a high intake of sodium chloride produced hypertrophy both in the heart and in the kidneys, even in the absence of a rise in blood pressure. Salt also remarkably increased the urinary calcium excretion. These harmful effects of salt were blocked by the thiazide diuretic hydrochlorothiazide but not by the ACEI enalapril. However, this study does not allow to make any direct comparison between the effects of enalapril and hydrochlorothiazide.
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PMID:Effects of enalapril and hydrochlorothiazide on the salt-induced cardiac and renal hypertrophy in normotensive rats. 784 79

Recent studies have shown that angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR) reduces blood pressure into adulthood. This study explored changes in vascular reactivity in adult normotensive (WKY) rats and stroke-prone SHR (SHRSP) receiving the following treatments at 6-10 weeks of age: (a) ACE inhibitor (ramipril); (b) hydralazine/hydrochlorothiazide (hydral/HCTZ); or (c) no treatment. The hypothesis tested was that vascular changes and blood pressure would be reduced in adult SHRSP treated with ramipril during development. At 17 weeks of age, rats were anesthetized and vascular tissue was excised. Isolated experiments in the aorta included characterization of initial phasic and tonic contractions to 0.1 microM angiotensin II (AII). A phenylephrine (PE) concentration-response curve was performed on carotid arteries, and threshold values were determined. All WKY groups showed lower systolic blood pressure (131 +/- 4 mmHg) and reduced phasic AII induced contraction (7.4 +/- 4.7%) compared with SHRSP (217 +/- 4 mmHg; 37.2 +/- 4%). Antihypertensive treatment reduced blood pressure (ramipril: 168 +/- 2; hydral/HCTZ: 198 +/- 6 mmHg) but not phasic AII responses in adult SHRSP; adult WKY rats were unaffected by treatment. Threshold values for PE in carotid arteries were lower in SHRSP than in WKY, indicating increased sensitivity. However, SHRSP treated with ramipril did not demonstrate increased sensitivity to PE. These data support the hypothesis that blood pressure and sensitivity to PE but not contractile responsiveness to AII in adult SHRSP are determined by an AII-sensitive mechanism during development.
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PMID:Long-term effects of brief antihypertensive treatment on systolic blood pressure and vascular reactivity in young genetically hypertensive rats. 852 52

The general pharmacological properties of a combination of the angiotensin converting enzyme (ACE) inhibitor moexipril hydrochloride (CAS 82586-52-5) and the thiazide diuretic hydrochlorothiazide (CAS 58-93-5, HCTZ), ratio 7.5 + 12.5, were studied in generally accepted models in vitro and in vivo. In vitro, the combination showed neither agonistic nor antagonistic activities on the isolated guinea pig trachea in concentrations up to 2 x 10(-4) g/ml. In mice, there was no effect on intestinal motility or the thiopental-induced sleeping time up to 1000 mg/kg. The only activity observed in mice was an inhibition of spontaneous motility after oral dosing with 300 and 1000 mg/kg, respectively. Both HCTZ (1-10 mg/kg) alone and the combination moexipril/HCTZ (1.6 or 4.8 mg/kg) produced dose-related increases in diuresis and electrolyte excretion in rats, however, without any potentiating effects for the drug combination. On the cardiovascular system of anaesthetised dogs, the effects observed were as expected, e.g. dose-related decrease in blood pressure. Repeated dose toxicity studies in rats and dogs revealed the kidney as target organ. This effect, based on highly exaggerated pharmacological activity, is well-known for other ACE inhibitors. No potential for teratogenic effects could be observed for the drug combination. In summary, the preclinical data indicate that the combination of moexipril and HCTZ (ratio 7.5 + 12.5) represents a safe drug without relevant side effects or gross toxicity.
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PMID:Preclinical safety studies of the combination moexipril hydrochloride/hydrochlorothiazide. 960 78

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)). In addition to blood pressure (SBP, DBP), carotidofemoral pulse wave velocity (PWV) was assessed non-invasively. Total peripheral resistance (TPR) was determined from cardiac output derived by electrical impedance cardiography. Sitting DBP decreased for -14.4 mmHg following Vera/Tran compared with -9.2 mmHg following Meto/HCTZ (p = 0.02 for difference between treatments). Blood pressure was normalized (i.e. DBP < 90 mmHg) in 69% of patients with Vera/Tran and in 52% with Meto/HCTZ. PWV was lowered with Vera/Tran to a higher extent than with Meto/HCTZ (differences between group means -0.46 to -0.98 m/sec, statistically not significant). Vera/Tran induced a decrease in TPR of about 15% of baseline values, whereas Meto/HCTZ showed no influence. Treatment-related adverse events following Meto/HCTZ were bradycardia and associated symptoms; following Vera/Tran these were cough and edema in 1 case each. In the Meto/HCTZ group, there were more withdrawals/drop-outs (9/25) than in the Vera/Tran group (2/26). The somewhat more intense reduction in PWV with Vera/Tran is indicative of an increase in aortic elastic properties associated with the more potent decrease in BP. In the present study, the combination of calcium antagonist plus ACE inhibitor was found to be an effective and well tolerated antihypertensive regimen and in these respects appears to have some advantages compared with a combination of beta-blocker plus diuretic.
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PMID:Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy. 972 95

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.
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PMID:Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. 1021 6

The objective of the present study was to analyze the influence of the I/D polymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One hundred thirty-six essential hypertensive patients who were <50 years old and had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmacological treatment consisting of moderate salt restriction and a low-calorie diet they were obese, with or without a regimen of antihypertensive drugs based on beta-blockers or ACE inhibitors. Hydrochlorothiazide was added when necessary to maintain the blood pressure goal of <135/85 mm Hg. At the beginning of the study and at yearly intervals, systolic and diastolic blood pressures (SBP and DBP, respectively), 24-hour urinary albumin excretion (UAE), renal function, and biochemical profile measurements were made. The insertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistical analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specific regression line slope values. At baseline, no differences in blood pressure or UAE values were observed among genotypes. Likewise, the genotype or allele frequency was not significantly different between normoalbuminurics and microalbuminurics. After the 3 treatment years, significant reductions in SBP, DBP, and UAE were found (SBP 151.6+/-17.3 reduced to 137.2+/-14.3 mm Hg, P<0.001; DBP 96.6+/-8.9 reduced to 84.5+/-9.8 mm Hg, P<0.001; UAE 36.7+/-71.5 reduced to 28.3+/-78.6 mg/24 h, P<0. 05). The slopes of these parameters over time did not differ significantly among genotypes. The slope of SBP was the main factor related to the slope of logUAE (P<0.003). A significant positive correlation coefficient between the SBP and logUAE slopes was observed for the DD patients (r=0.57, P<0.0001) but was absent in patients carrying the I allele (II r=-0.03, P=NS; I/D r=0.01, P=NS). Follow-up studies should be used to achieve a better understanding of the impact of candidate gene polymorphisms on the development of hypertension-induced organ damage. Assessment of the I/D polymorphism of the ACE gene may identify subjects who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertension-associated complications and death.
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PMID:Influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the outcome of microalbuminuria in essential hypertension. 1064 47

In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the authors assessed the potential for BP control using hydrochlorothiazide (HCTZ, 12.5 mg daily), given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension (mean day diastolic blood pressure [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3 monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall, profound and sustained BP reduction was observed at the end of the study. The 24-hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p < 0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/- 14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs. baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial 12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained controlled at 6 months and only 1 patient at 12 months. In contrast, quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months, with a significant number of patients (22/49, 45%) requiring the highest dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment, with most patients requiring the addition of the ACE inhibitor.
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PMID:Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension. 1088 12

Despite the recent emphasis on combination drug therapy for hypertension, little attention has been given to alpha/beta blockade using agents other than labetalol. The purpose of this study was to 1) compare the efficacy of low-dose alpha/beta blockade using doxazosin + betaxolol, versus monotherapy with an angiotensin converting enzyme inhibitor (quinapril) and a diuretic (hydrochlorothiazide [HCTZ]), and 2) assess the efficacy of low-dose doxazosin. In a crossover study, 21 hypertensive subjects were treated for 3 weeks each with HCTZ, 12.5 to 25 mg/day, quinapril, 10 to 40 mg/day, and a combination of doxazosin, 1 to 4 mg + betaxolol, 5 to 10 mg daily. Doses were titrated to achieve a systolic pressure <130 mm Hg, as assessed by self-recorded home measurements. Home blood pressure decreased 11.5/7.5 mm Hg after HCTZ, 12.9/8.8 mm Hg after quinapril, and 21.2/16.5 mm Hg after doxazosin + betaxolol (P < .001/< .001 v HCTZ and P < .002/< .001 v quinapril). The target systolic pressure was achieved by 33%, 43%, and 71% of subjects, respectively (P = .04 v HCTZ, and .03 v quinapril). Among the 8 subjects in whom doxazosin dosage was increased to the maximum of 4 mg, the mean blood pressure achieved at 4 mg did not differ from that achieved at 2 mg (136/87 v 136/88 mm Hg). We conclude that oral alpha/beta blockade is superior to monotherapy with an angiotensin converting enzyme inhibitor or a diuretic and that maximal or near maximal efficacy can be achieved at a 2-mg dose of doxazosin. Low-dose oral alpha/beta blockade merits greater consideration in the drug therapy of essential hypertension.
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PMID:Low-dose alpha/beta blockade in the treatment of essential hypertension. 1141 35

This double-blind placebo-controlled study was designed to investigate the acute and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide excretion, and several components of the renin-angiotensin system were measured for 6 hours on days 1 and 7 of drug administration. When compared with the placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease in plasma angiotensin II levels (P<0.001 versus placebo; P<0.05 versus FOS/HCTZ) and an increase in urinary atrial natriuretic peptide excretion (P<0.01). These hormonal effects were associated with a significant fall in blood pressure (P<0.01) and a marked renal vasodilatation, but with no significant changes in glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium excretion (P<0.001). The acute natriuretic response to FOS/HCTZ was significantly greater than that observed with omapatrilat (P<0.01). Over 1 week, however, the cumulative sodium excretion induced by both doses of omapatrilat (P<0.01 versus placebo) was at least as great as that induced by the dose of FOS/HCTZ (P=NS versus FOS/HCTZ). In conclusion, the results of the present study in normal subjects demonstrate that omapatrilat has favorable renal hemodynamic effects. Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which explains its well-documented potent antihypertensive efficacy.
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PMID:Renal hemodynamic and natriuretic effects of concomitant Angiotensin-converting enzyme and neutral endopeptidase inhibition in men. 1221 65


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