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)

In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62-84 y, SBP greater than 160 mmHg, DBP greater than 100 mmHg, creatinine clearance 11-93 ml.min-1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0-24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol.l-1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.
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PMID:The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients. 133 May 74

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy]. 138 12

Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration.
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PMID:[Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril]. 145 52

1. The importance of total dose to the initial hypotensive response with an angiotensin converting enzyme inhibitor (quinapril) was assessed using a suggested 'maintenance' dose (20 mg) or matched placebo in a randomised double-blind study in patients with uncomplicated hypertension. 2. Thirty-two patients were recruited who were not on therapy or had not received diuretic therapy in their existing drug treatment in the preceding 4 weeks. Secondary causes of hypertension had previously been excluded and sustained clinic blood pressures of SBP greater than 160 mmHg and/or DBP greater than 90 mmHg were taken as indications for a trial of adjuvant or monotherapy with an ACE inhibitor. 3. After uneventful supervised therapy with quinapril in an open pilot study (n = 5) 27 patients entered a double-blind, randomised, crossover study of quinapril or placebo using ambulatory monitoring to assess BP response. 4. All patients remained asymptomatic and both therapy and monitoring were well tolerated. A smooth onset of antihypertensive effect was noted with an overall 24 h placebo corrected fall in systolic BP of 9.9 mmHg (7.2-12.6 95% CI) and diastolic BP of 6.4 mmHg (4.2-8.8) with no significant effect on heart rate. Individual placebo corrected maximal responses during the first 8 h following quinapril showed a wide range for both systolic (+1.56 to 44.0 mmHg) and diastolic (+2.3 to -35.6 mmHg) pressure. Larger falls tended to be associated with higher baseline pretreatment pressures but in no case did absolute systolic pressure fall below 100 mmHg during the first 8 h following administration of placebo or quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response to the first dose of an angiotensin converting enzyme inhibitor in uncomplicated hypertension--a placebo controlled study utilising ambulatory blood pressure recording. 177 77

The safety and efficacy of lisinopril in the treatment of mild to moderate essential hypertension was evaluated by Belgian general practitioners in patients whose hypertensive condition remained uncontrolled by previous treatment and/or in whom the prior drug regimen was not tolerated. In this 8-week study, 3060 eligible patients were initially treated with 20 mg lisinopril once daily; this dose was increased to 40 mg if diastolic blood pressure (DBP) was greater than 90 mm Hg after 4 weeks. Lisinopril monotherapy in the 1902 patients completing the trial resulted in marked reductions of systolic (SBP) and DBP from 172.5/102.4 mm Hg at baseline to 147.4/86.6 mm Hg by week 8. More than 90% of patients achieved a DBP less than 95 mm Hg. The decrease in blood pressure was similar in patients older and younger than 65 year of age. Only about 20% of patients required an increase in their daily intake of lisinopril to 40 mg. Treatment was well tolerated and the profile of adverse events was similar to the pattern found with other nonsulfydryl angiotensin converting enzyme inhibitors. Tolerance in the elderly was similar to that experience by hypertensives under 65 years of age. Thus, lisinopril at 20 or 40 mg once daily proved both well tolerated and effective in reducing blood pressure in patients with mild to moderate essential hypertension.
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PMID:The antihypertensive effect and safety of lisinopril in patients with mild to moderate essential hypertension. A Belgian multicenter study. 217 13

ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents.
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PMID:Systolic hypertension in the elderly: controlled or uncontrolled. 218 67

In order to determine the dose regimen of new antihypertensive compounds, between-patient trials are usually performed. However, the combined use of a crossover design and a precise methodology to measure blood pressure (BP) and biological effects can provide relevant data with a minimal number of patients, if there is no carryover effect which invalidates the experiment. Such goals were successfully achieved with just 25 hypertensive patients who were randomly allocated in double-blind fashion every 2 weeks to a new angiotensin converting enzyme (ACE) inhibitor, benazepril [10 mg once a day (o.d.), 20 mg o.d., 10 mg twice a day (b.i.d.) and 20 mg b.i.d.], or a placebo. The mean BP fall [systolic (SBP)/diastolic (DBP), measured in mmHg] just before drug intake was significantly greater with benazepril: -14/-9 (10 mg o.d.); -15/-8.5 (20 mg o.d.); -22.5/-14 (10 mg b.i.d.), and -21/-13 (20 mg b.i.d.) in comparison with placebo (-3/-3). Mean active plasma renin (measured in pg/ml), assessed by an immunoradiometric assay based on two monoclonal antibodies, increased significantly in a dose-dependent manner, by +0.7 (placebo), +15.0 (10 mg o.d.), +23.4 (20 mg o.d.), +44.4 (10 mg b.i.d.) and +78.8 (20 mg b.i.d.), whereas plasma ACE decreased (by 67 and 78% after 10 and 20 mg o.d., respectively, and by 91-92% after 10 and 20 mg b.i.d.). In the clinical development of an antihypertensive drug, the earlier use of such within-patient studies, with the random insertion of one placebo period between the active periods, should help in the dose-response curve search.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Crossover design for the dose determination of an angiotensin converting enzyme inhibitor in hypertension. 269 28

Cardiac performance, as judged by preload, afterload, and myocardial contractility, was evaluated by non-invasive M-mode echocardiography before and after acute oral administration of calcium entry blockers (nitrendipine and verapamil), angiotensin converting enzyme (ACE) inhibitors (captopril and lisinopril), and a dopamine receptor agonist (fenoldopam) in patients with mild to moderate essential hypertension. Left ventricular end diastolic volume was taken as an index of preload, end systolic stress as an index of afterload, and the ratio of systolic pressure to end systolic volume (SBP:ESV), ejection fraction (EF), and mean velocity of circumferential fibre shortening (Vcf) as indices of contractility. Reductions of afterload and mean arterial pressure were achieved with all antihypertensive agents involved (mean percentage change +/- s.e.m.: 15 +/- 2% and 10 +/- 1%, respectively, P < 0.05) but the afterload reduction with lisinopril was greatest (21 +/- 9%; P < 0.01). The dopamine receptor agonist fenoldopam decreased by preload 24% (P < 0.05) and increased all of the three parameters of myocardial contractility (SBP:SV 66%; EF 17%, Vcf 19%; P < 0.01). In contrast, no effect on these parameters was observed with either calcium entry blocker or either ACE inhibitor.
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PMID:Disparate cardiac effects of afterload reduction in hypertension. 285 42

Effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219) a new orally active angiotensin converting enzyme (ACE) inhibitor, on cardiovascular system in experimental animals were examined. In conscious renal hypertensive dogs, alacepril (3 mg/kg p.o.) caused a marked reduction in systolic and diastolic blood pressure (SBP and DBP) and total peripheral vascular resistance (TPR), but did not change significantly heart rate (HR), cardiac output (CO), stroke volume (SV), cardiac work (CW) and electrocardiogram (ECG). Captopril (3 mg/kg, p.o.) showed similar changes in cardiovascular parameters as alacepril. In anesthetized open-chest normotensive dogs, alacepril (3-100 micrograms/kg/min for 10 min, i.v. infusion) tended to decrease DBP and TPR, but did not change significantly CO, stroke work (SW), left ventricular end diastolic pressure (LVEDP), dp/dt and HR. Captopril also showed similar effects but these changes were greater in extent than those of alacepril. In conscious renal hypertensive rats, alacepril did not affect the regional cerebral blood flow in the frontal cortex and the dorsal hippocampus after single (3 and 10 mg/kg) and successive (3 mg/kg/d for 7 days) oral administration. Captopril (10 mg/kg) significantly decreased blood flow in the frontal cortex after single oral administration. In conscious normotensive dogs, alacepril (3 and 30 mg/kg p.o.) increased renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and urinary Na+/k+ ratio, but did not change glomerular filtration rate (GFR) and urinary potassium excretion (UKV). Captopril (3 and 30 mg/kg p.o.) also showed similar changes as alacepril. These effects of alacepril on cardiovascular system resemble those of captopril and might be considered as a favourable profile for the antihypertensive agent.
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PMID:Effect of the novel orally active angiotensin converting enzyme inhibitor alacepril on cardiovascular system in experimental animals. 351 79

Thirty elderly, mildly hypertensive patients were enrolled for a single-blind, randomised cross-over placebo controlled trial in which placebo and lisinopril (20 mg/day before breakfast) were given for 4 and 8 weeks, respectively. A wash-out period of 3 weeks between placebo and lisinopril was observed. In each patient a euglycaemic glucose clamp with simultaneous indirect calorimetry allowed us to determine whole body glucose disposal and substrate oxidation. Changes in morning SBP and DBP were also determined. Lisinopril vs. placebo significantly improved whole body glucose disposal (40.4 +/- 0.4 vs. 30.3 +/- 0.4 mumol/kg LBM x min; P < 0.01), non-oxidative glucose metabolism (18.1 +/- 0.7 vs. 10.9 +/- 0.6 mumol/kg LBM x min; P < 0.01) and fasting plasma potassium levels (4.8 +/- 3 vs. 4.4 +/- 0.4 mmol/l; P < 0.05). SBP (175 +/- 3.3 vs. 160 +/- 3.0 mm Hg; P < 0.001) and DBP (106 +/- 2.3 vs. 95 +/- 2.0 mm Hg; P < 0.001) were significantly reduced by lisinopril administration. After ACE inhibition, fasting plasma potassium levels correlated with the decline in mean arterial BP (r = -0.71; P < 0.006). In conclusion, lisinopril administration reduces arterial BP and improves insulin sensitivity in elderly hypertensive patients.
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PMID:Lisinopril administration improves insulin action in aged patients with hypertension. 756 82


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