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 aim of this 16-week trial was to determine the safety and efficacy of a step-care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6-week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The French multicentre study of ramipril in ambulatory patients with mild-to-moderate hypertension. 130 60

Ramipril is a long acting angiotensin converting enzyme (ACE) inhibitor, which exhibits similar pharmacodynamic properties to Captopril and Enalapril. Like Enalapril, it is a prodrug, which is hydrolyzed after absorption to form the active metabolite ramiprilat which has a long elimination half-life, permitting once daily administration. In the dose range 2.5-10 mg once daily the drug has been effective and well tolerated during treatment for up to two years. In dosages of 5 or 10 mg once daily the antihypertensive efficacy of Ramipril was comparable with usual therapeutic dosages of Captopril, Enalapril, and Atenolol.
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PMID:Ramipril: a review of the new ACE inhibitor. 153 70

Felodipine induces natriuresis, possibly by renal hemodynamic and/or tubular effects. Theoretically, reversal of the sodium-retaining effect of angiotensin II (Ang II) could be involved. Therefore, we administered felodipine during Ang II infusion and during suppression of endogenous Ang II production in two double-blind studies in healthy volunteers. First, a gradually increasing dose of Ang II was infused during felodipine or solvent infusion. Before starting Ang II, felodipine had lowered renal vascular resistance (RVR) and filtration fraction (FF), and simultaneously increased CNa. The Ang II induced rise of mean arterial pressure (MAP) and renal vasoconstriction was partly antagonized and the falls in glomerular filtration rate (GFR) and CNa completely abolished by felodipine. The combination of felodipine and 3.0 ng/kg/min Ang II even enhanced natriuresis. Second, felodipine or solvent was infused after one week of pretreatment with placebo or the angiotensin converting enzyme (ACE) inhibitor ramipril, which reduced MAP and induced renal vasodilatation. Ramipril pretreatment did not influence significantly the blood pressure reduction, renal vasodilatation, and natriuresis caused by felodipine. In conclusion, it seems unlikely that the natriuretic effect of felodipine is due to interference with renal effects of endogenous Ang II. The fact that felodipine reverses sodium retention on exogenous Ang II may be explained by interference with systemic and renal hemodynamic effects of exogenous Ang II.
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PMID:Is natriuresis on felodipine due to reversal of the renal effects of angiotensin II? 153

1. The possibility of an acute pharmacokinetic or pharmacodynamic interaction between the ACE inhibitor ramipril and the calcium antagonist felodipine was examined in 12 normotensive male volunteers. 2. Ramipril (5 mg) and felodipine ER (10 mg) were administered orally in a double-blind, randomised, placebo-controlled, Latin square design to fasting subjects. 3. There was no evidence of a pharmacokinetic interaction between agents. The concentration-time profiles remained unaltered by coadministration of both agents. 4. Plasma ACE inhibition by ramiprilat was unaffected by concurrent felodipine. The trend towards increased fractional sodium excretion after felodipine was not influenced by ramipril. Plasma renin activity, aldosterone and catecholamines remained unaltered. 5. Combination therapy produced a statistically significant fall in blood pressure supine and erect which was not evident with monotherapy. The reflex tachycardia associated with felodipine monotherapy was significantly attenuated by the coadministration of ramipril. 6. This study presents further evidence for the effective combination of ACE inhibitors and calcium antagonists to lower blood pressure. The reflex tachycardia associated with calcium antagonist therapy can be significantly reduced by coadministration with sustained antihypertensive effect.
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PMID:A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects. 164 21

Six double-blind studies were designed to assess the efficacy, tolerance, and safety of the angiotensin-converting enzyme inhibitor ramipril in patients with mild-to-moderate essential hypertension. Of 1,189 hypertensive patients in these studies, 105 patients were diabetic. They were randomly assigned either to a ramipril monotherapy group (1.25-10 mg/day) or to one of the following treatment groups: ramipril (5 mg/day) plus piretanide (3 mg/day), captopril (100 mg/day), enalapril (10-20 mg/day), hydrochlorothiazide (50 mg/day), or atenolol (100 mg/day). In all studies, a 4-week single-blind placebo run-in phase was followed by a 6-week double-blind active treatment phase. Significant reductions in blood pressure were achieved with all antihypertensive agents. No statistically significant deleterious effects were observed on concentrations of blood glucose, although diabetics who received hydrochlorothiazide showed slight increases in blood glucose levels. Ramipril was well tolerated by diabetic patients, and no serious adverse events occurred. Adverse events reported were typical of ACE inhibitors.
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PMID:Assessment of the efficacy, tolerance, and safety of ramipril in diabetic patients with mild-to-moderate hypertension: a retrospective analysis. 172 32

To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.
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PMID:Salt blocks the renal benefits of ramipril in diabetic hypertensive rats. 182 92

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetics is controversial. In order to dissociate the hypotensive and intrarenal effects, 16 insulin-dependant diabetics with permanent microalbuminuria (30-300 mg/24 h) without hypertension were given Ramipril, a long acting ACE inhibitor, at hypotensive (treatment A 5 mg/day; N = 8) and at sub-hypotensive doses (treatment B, 1.25 mg/day; N = 8) over a 6 week period in parallel double-blind study. Blood pressure, UAE, glomerular filtration renal blood flow (continuous 125I-Iodothalamate + 131I-Hippurate infusion) and converting enzyme activity (Liebermann's method), before and after treatment. In treatment group A, the blood pressure fell from 133 +/- 5/79 +/- 4 (mean +/- SE) to 125 +/- 4/77 +/- 2 mmHg (p less than 0.05 for systolic blood pressure) whereas it remained stable in treatment group B (132 +/- 7/79 +/- 4 to 128 +/- 5/80 +/- 4 mmHg). The UAE decreased in both groups: group A from an average of 74 (40-198) to 47 (5-202) mg/24 h (p = 0.07; group B, from an average of 77 (50-136) to 19 (15-120) mg/24 h (p less than 0.005), as did ACE activity: group A from 332 +/- 44 to 163 +/- 33 iu/l (p less than 0.004), group B from 423 +/- 39 to 191 +/- 28 iu/l (p less than 10-4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dissociation of hypotensive and renal hemodynamic effects of an angiotensin converting enzyme inhibitor in insulin-dependent diabetic patients with incipient nephropathy]. 182 59

Cardiac hypertrophy of various aetiologies is consistently associated with increased expression of V3 isomyosin. Uraemia is associated with cardiac hypertrophy. In the present study, we examined regulation of isomyosin in uraemic rats, using gel electrophoresis. Cardiac hypertrophy in uraemic animals was associated with a relative increase in V1 isomyosin. An increased proportion of V1 isomyosin was demonstrable 3 days after subtotal nephrectomy (NX 63.0 +/- 8.8%; control 43.6 +/- 7.2%; P less than 0.01) and persisted during uraemia of 80 days duration. Elevation of V1 isomyosin, relative to pair-fed controls, was observed in uraemic animals of various age. The proportion of V1 isomyosin changed in the same direction as controls when several manouevers were used which changed the isomyosin pattern, but the difference between uraemic animals and controls persisted. We studied the effect of carbohydrate loading or deprivation, starvation or administration of energetically inadequate diets, castration or administration of androgens and sodium depletion. With each of the above interventions, a difference between subtotally nephrectomized animals and sham-operated pair-fed control animals was statistically significant (P less than 0.05). Elevation of V1 isomyosin persisted during combined alpha and beta blockade and was still found when blood pressure was normalized by ACE inhibition using Ramipril. It is concluded that cardiac hypertrophy of uraemia differs from all other forms of cardiac hypertrophy by the occurrence of increased proportion of V1 isomyosin. The proportion of V1 isomyosin responds adequately to regulatory signals but is set at an abnormally high level.
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PMID:Regulation of myocardial isomyosin V1 in uraemic rats. 183 Aug 44

Ramipril is a new, potent nonsulfhydryl inhibitor of angiotensin converting enzyme. The magnitude and duration of its antihypertensive effect were evaluated in a multicenter, placebo-controlled, randomized clinical trial conducted in 100 patients with mild to moderate essential hypertension. Ramipril significantly reduced both supine and standing blood pressures measured 24 h after dosing. Automated blood pressure monitoring showed that ramipril significantly reduced systolic and diastolic pressures for 24 h after dosing. The peak effect occurred between 3 and 6 h after dosing, with approximately 50% of this effect retained after 24 h. Ramipril was well tolerated; there was no significant difference between active drug and placebo in the overall incidence of side effects. Ramipril is an effective and well-tolerated antihypertensive agent, which reduces both supine and standing blood pressure over the entire 24-h period after dosing.
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PMID:24-hour blood pressure profiles in hypertensive patients administered ramipril or placebo once daily: magnitude and duration of antihypertensive effects. Ramipril Multicenter Study Group. 183 14

The aim of this study was to determine the acute and chronic arterial effects of the ACE inhibitor, ramipril. Fourteen patients (mean age 47 years) with mild to moderate essential hypertension completed the study. A first haemodynamic examination was performed at the end of a 15-day placebo period (D15) before and 3 hours after oral administration of ramipril, 5 mg. Then all the patients started a 4-week treatment with ramipril, 5 mg/day. At the end of this period (D42) the haemodynamic examination was repeated 24 hours after the last capsule intake, and then 3 hours after administration of ramipril 5 mg. Brachial and carotid artery haemodynamics were evaluated by a bidimensional pulsed Doppler system. Arterial distensibility was non-invasively studied in three different arterial segments (carotido-femoral, brachio-radial, femoro-tibial) by the evaluation of the pulse wave velocity. Ramipril significantly decreased BP after acute or chronic administration. Chronic treatment with ramipril was followed by a long lasting increase in brachial artery diameter, a decrease in forearm vascular resistance, and an improvement in aortic distensibility. The other investigated arterial segments did not show any significant changes. Our results suggest that long lasting arterial effects of the ACE inhibitor ramipril are partly pressure-independent and are related to an effect of this drug on arterial tone. These effects may be able to reduce the hypertensive cardiac and arterial abnormalities.
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PMID:Long lasting arterial effects of the ACE inhibitor ramipril. 183 63


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