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)

Amlodipine is a dihydropyridine calcium antagonist which can be used once daily in hypertension. The pharmacokinetics of the molecule mean that effective blood levels and hence good control of blood pressure are maintained throughout the dosing interval. Dose-ranging studies have shown the most appropriate starting dose is 5 mg once daily, with simple adjustment to 10 mg if necessary. Comparative studies with other agents have shown amlodipine to have antihypertensive efficacy superior to verapamil and comparable with atenolol, hydrochlorothiazide, captopril or nitrendipine. When used in combination with angiotensin converting enzyme inhibitors, beta-blockers or thiazide diuretics, amlodipine can produce important additional antihypertensive effects. Studies involving long-term use of amlodipine in hypertension indicate that no tolerance appears, and that amlodipine is a well tolerated drug.
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PMID:Amlodipine: an effective once-daily antihypertensive agent. 183 48

The database on amlodipine, a calcium antagonist of the 1,4-dihydropyridine class, was obtained from clinical trials in the United States, Canada, and Europe. The clinical dossier describing the efficacy and safety of once-daily amlodipine in the treatment of hypertension is extensive, well organized, and logically designed. It shows that amlodipine is an effective antihypertensive drug, providing smooth 24-h blood pressure control without orthostatic hypotension, and that it is well tolerated as monotherapy and in combination with other antihypertensive drugs. A total of 18 clinical studies were reviewed; 1,091 patients received amlodipine whereas 805 received either placebo or another drug for comparison. The common entry criteria include a supine and standing diastolic blood pressure in the range 95-114 mg Hg. Blood pressure measurements were made 24 h after the last dose of amlodipine in all studies. Amlodipine is clearly superior to placebo and induces a clinically significant reduction in blood pressure (mean reductions 23/13 mm Hg supine, 24/12 upright in one representative study) with similar heart rates in the supine and standing positions. Blood pressure control shows a smooth profile over 24 h with once-daily dosing, and there is no tolerance with long-term administration of the drug. The useful clinical dose is in the range of 5-10 mg, which is well tolerated in comparison with clinical doses of atenolol, hydrochlorothiazide, or verapamil. Amlodipine can be used as monotherapy in a large proportion of patients but may also be combined with a beta-blocker, diuretic, or angiotensin converting enzyme inhibitor. Based on these observations, amlodipine may prove to be an attractive addition to our antihypertensive armamentarium.
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PMID:Amlodipine in hypertension: an overview of the clinical dossier. 246 23

The efficacy, tolerability and impact on quality of life of amlodipine and enalapril were compared in a multicentre, double-blind, general practice study in 461 mild and moderate hypertensives over a 50-week active treatment period. Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were found to be similarly effective in lowering blood pressure while not adversely affecting quality-of-life parameters. However, 20% of the enalapril group compared with 11% of the amlodipine group required the addition of hydrochlorothiazide for blood pressure control (P < 0.01). Diastolic blood pressure was normalised or reduced by 10 mmHg in 204 (90%) patients on amlodipine and in 190 (85%) patients on enalapril. Side-effects were, in general, mild or of little clinical significance. The major side-effects recorded were class-typical of ACE inhibitors and calcium antagonists, namely cough (enalapril) and oedema (amlodipine), respectively. Tolerability was very good, with only 17 patients (8 amlodipine, 4%; 9 enalapril, 4%) being withdrawn from the study due to side-effects definitely related to treatment. Amlodipine monotherapy produced a slightly beneficial effect on blood lipid concentration, and both drugs reduced the calculated 10-year risk of coronary heart disease. It was concluded that the calcium antagonist amlodipine compared favourably with the ACE inhibitor enalapril in terms of antihypertensive efficacy, tolerability and impact on quality of life.
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PMID:A long-term, double-blind, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study. 803 5

Amlodipine belongs to the dihydropyridine class of calcium channel blockers. Both short and long term studies indicate that amlodipine effectively lowers mild to moderately elevated blood pressure and relieves symptoms of angina pectoris. In comparative studies, its antihypertensive efficacy is similar to that of other established agents such as beta-blockers, diuretics, ACE inhibitors and other calcium channel blockers (including the dihydropyridines); limited comparative data are, however, available in patients with angina pectoris. Amlodipine may offer potential in patients with congestive heart failure. Vasodilator adverse events such as oedema, headaches, and flushing are commonly observed with amlodipine. The drug does not appear to cause postural hypotension, reflex tachycardia or cardiac conduction disturbances. Comparative studies suggest that amlodipine is at least as well tolerated as other standard agents. Thus, amlodipine provides an attractive therapeutic option for the treatment of hypertension, and offers potential for patients with angina pectoris. Its beneficial effects in patients with congestive heart failure require confirmation in future studies.
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PMID:Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. 852 73

1. This study was undertaken to determine whether the AT1 receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2. Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1, receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3. Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level. 4. Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01). 5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP, TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on left ventricular hypertrophy and gene expressions of SHRSP were similar to those of losartan, except for the lack of inhibition of collagen type I expression by enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant difference between losartan and amlodipine in the effects on non-hypertrophied right ventricular gene expressions of SHRSP. 8. Our results show that hypertension causes not only left ventricular hypertrophy but also molecular transition of myocardium to a foetal phenotype and interstitial fibrosis-related molecular changes. These hypertension-induced left ventricular molecular changes may be at least in part mediated by the direct action of local angiotensin II via the AT1, receptor.
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PMID:Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats. 876 77

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.
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PMID:Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy induced in rats by prolonged inhibition of nitric oxide synthesis. 965 29

Double-blind, randomized controlled studies of longer than 1 week in duration comparing the antiproteinuric potential of long-acting dihydropyridine calcium channel blockers with that of angiotensin converting enzyme (ACE) inhibitors are lacking. Therefore, we performed such a study in patients with nondiabetic renal disease and proteinuria. After a 4-week wash-out period in which patients did not use any medication known to affect proteinuria, 21 patients were randomized in a double-blind fashion to receive either the calcium channel blocker amlodipine (Amlo, 5 to 10 mg) or the ACE-inhibitor lisinopril (Lis, 5 to 10 mg). Throughout the 16-week study period, blood pressure, creatinine clearances, and proteinuria were measured every 2 weeks. In addition, device-measured blood pressure and renal hemodynamic studies were performed at the start and end of the study. Systolic blood pressure fell in the Lis group from 163+/-7 (SEM) to 140+/-8 mm Hg (P < .01) and from 157+/-10 to 147+/-6 mm Hg in the Amlo group; diastolic blood pressure fell from 101+/-3 to 86+/-7 mm Hg in the Lis group and from 98+/-3 to 91+/-2 mm Hg in the Amlo group. Renal hemodynamics were not affected by amlodipine treatment, whereas a fall in glomerular filtration rate (GFR) was seen in lisinopril-treated patients (from 55+/-11 to 50+/-10 mL/min; P < .01). Amlodipine did not significantly affect proteinuria. Lisinopril induced a decline in the protein-creatinine ratio with a maximal effect reached after 12 to 16 weeks of therapy (from 0.39+/-0.17 to 0.26 +/-0.11 g/mmol; P < .009). In conclusion, we could not demonstrate an antiproteinuric effect of the long-acting dihydropyridine calcium channel blocker amlodipine, whereas therapy with the ACE-inhibitor lisinopril resulted in a decrease in proteinuria. Amlodipine did not affect renal hemodynamics, whereas lisinopril induced a fall in GFR.
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PMID:Comparison between the effects of amlodipine and lisinopril on proteinuria in nondiabetic renal failure: a double-blind, randomized prospective study. 975 92

Recent trials have linked calcium antagonists with adverse cardiovascular events in hypertensive patients with diabetes. A closer examination of these trials (in particular the Appropriate Blood Pressure Control in Diabetes [ABCD] trial and the Fosinopril Versus Amlodipine Cardiovascular Events Trial [FACET]) reveals a lack of data from which to draw conclusions of harm. In fact, based on the results of these trials and the recent Hypertension Optimal Treatment (HOT) Trial, one may conclude that the combination of a calcium antagonist with an ACE inhibitor is a rational therapeutic choice in patients with coexisting hypertension and diabetes.
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PMID:Calcium antagonists and cardiovascular risk in diabetes. 982 45

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/- SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P = .01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.
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PMID:A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients. 1019 33

Mibefradil and amlodipine are calcium antagonists with different channel selectivities. Mibefradil blocks both L- and T-type calcium channels; although in the usual pharmacological doses, it predominantly blocks the T-type channels. In contrast, amlodipine selectively blocks L-type channels. The goal of the present study was to assess whether this differential selectivity would result in different effects on end-organ damage in experimental hypertension. For this purpose, deoxycorticosterone acetate (DOCA)-salt hypertensive rats were treated either with equipotent doses of mibefradil or amlodipine (30 mg. kg(-1). d(-1) as food admix). Despite the fact that both drugs decreased systolic arterial pressure to the same extent (140+/-5 mm Hg in the mibefradil group and 144+/-3 mm Hg in the amlodipine group versus 225+/-5 mm Hg in the untreated-DOCA group), only mibefradil decreased proteinuria (35. 5+/-6.5 versus 103.3+/-14.1 mg/24 h in untreated DOCA-salt animals) and prevented glomerular lesions. Both drugs, however, prevented the occurrence of vascular renal lesions. To elucidate the mechanism responsible for this difference, we evaluated in an additional series of experiments the effects of mibefradil and amlodipine on plasma and renal renin concentrations, as well as the effects of the addition of enalapril, an ACE inhibitor, given on top of both drugs on proteinuria. Amlodipine, in contrast to mibefradil, markedly stimulated the plasma (17.8+/-2.6 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 3.9+/-0.4 ng Ang I. mL(-1). h(-1) in the mibefradil group and 3.2+/-0.3 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) and renal (2.42+/-0.37 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 0.36+/-0.04 ng Ang I. mL(-1). h(-1) in the mibefradil group and 0.26+/-0.08 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) renin concentrations. Stimulation of the renin-angiotensin system could explain the absence of a renal protective effect of amlodipine. This was also suggested by the fact that enalapril given in addition to amlodipine could decrease proteinuria. In conclusion, T-type channel blockade by mibefradil decreases blood pressure without stimulation of the renin-angiotensin system and therefore prevents most of the glomerular damage in DOCA hypertensive rats.
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PMID:Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats. 1052 45


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