Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lisinopril is a potent competitive inhibitor of purified rabbit lung ACE (dissociation t1/2 = 105 min). To examine reversibility of binding and ACE functional activity in situ, the single-pass extraction (E) of an 125I-lisinopril analogue (351A) and the hydrolysis of an ACE substrate, benz-phe-ala-pro (BPAP) were studied. Lungs were perfused at 50 ml/min with a Krebs-albumin (3%) solution. A bolus containing [14C]dextran, [3H]BPAP, and 351A was injected and (E)351A measured by multiple indicator dilution technique. BPAP metabolism (M) was reflected by the appearance of its hydrolysis product [3H]benz-phe in lung effluent. Control (E)351A was 66 +/- 5% (mean +/- SD, n = 6) and (M)BPAP was 69 +/- 9% (n = 6). Unlabeled lisinopril (30 nmol) in the bolus significantly reduced E(351A) and M(BPAP) to 16 +/- 16% and 3 +/- 3%, respectively. Ten minutes later E(351A) and M(BPAP) had returned to control values. Reduction of E(351A) was partially reversible and M(BPAP) completely reversible after 1 min. After recirculation with 0.25 mM lisinopril for 30 min, however, significant depression of E(351A) was evident for 60 min after exposure to lisinopril was discontinued. Thus, rapid as well as slowly reversible components of inhibition of ACE inhibitor binding can be demonstrated in the perfused rabbit lung.
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PMID:Rapid reversal of angiotensin converting enzyme inhibition by lisinopril in the perfused rabbit lung. 131 50

The effects of doxazosin (alpha-1-inhibitor) and enalapril (ACE-inhibitor) on blood pressure and exercise stress test were assessed in 10 hypertensive patients (8 M, 2 F, age 58 +/- 9 years) with coronary artery disease and exertional myocardial ischemia. A single blind, cross-over, placebo controlled trial was performed. Placebo was administered for 2 periods of 2 weeks, doxazosin and enalapril for at least 3 weeks. The sequence of the active drugs was randomized and the single daily dose, obtained by titration, was 7 +/- 5 mg for doxazosin and 18 +/- 13 mg for enalapril. Blood pressure measurements and treadmill tests (Bruce protocol) were performed at the end of each period. Rest systolic and diastolic pressures after placebo were respectively 173 +/- 15 and 106 +/- 9 mmHg and were reduced to 153 +/- 11 and 93 +/- 12 mmHg (p less than 0.05) after doxazosin and to 150 +/- 24 and 93 +/- 12 mmHg (p less than 0.05) after enalapril. Total exercise time was 473 +/- 91 s after placebo and increased to 545 +/- 84 s (p less than 0.05) after doxazosin and 529 +/- 100 s (p less than 0.05) after enalapril. Time to 1 mm ST depression (ST1) was 297 +/- 102 s after placebo and increased to 414 +/- 96 s (p less than 0.05) after doxazosin and to 396 +/- 133 s (p less than 0.05) after enalapril. Double product at peak exercise and at ST1 were respectively 26.3 +/- 2.8 and 22.1 +/- 2.8 x 10(3) and remained unchanged after enalapril and doxazosin. Peak exercise diastolic blood pressure was 107 +/- 5 mmHg after placebo, was reduced to 94 +/- 15 mmHg (p less than 0.05) after doxazosin and was unchanged after enalapril (101 +/- 10 mmHg, NS). Thus, doxazosin and enalapril induced a comparable decrease of rest blood pressure and a similar increase of exercise time in hypertensive patients with exertional myocardial ischemia. Doxazosin but not enalapril reduced exercise diastolic blood pressure.
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PMID:[Comparative effects of doxazosin and enalapril in patients with arterial hypertension and exercise-induced acute myocardial ischemia]. 168 51

The aim of this study was to evaluate the anti-ischemic efficacy of 2 different doses of benazepril (B), a new ACE-inhibitor, 10 and 20 mg, given per os. Fifteen male patients gave informed, written consent; they were aged 40-67 years, with stable effort angina pectoris and were randomly given, in double-blind condition, a tablet containing B 10 mg, B 20 mg or placebo (PL), once a day, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the same day, 2 and 10 hours after the last drug intake. B 10 mg and B 20 mg, in patients with stable effort angina, compared to placebo, increased ischemic threshold and decreased ischemic ST depression at maximal work, after 2 hours but not after 10 hours. In conclusion B 10 mg and B 20 mg showed anti-ischemic activity 2 hours after drug intake.
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PMID:[Effects of benazepril, a new ACE inhibitor, in effort angina pectoris]. 179 89

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.
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PMID:The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo. 181 Aug 15

To investigate the potential anti-ischaemic effects of benazepril (10 mg bid) in comparison to placebo, this new ACE-inhibitor was given to 11 patients with chronic stable angina, reproducible exercise-induced ST-segment depression and angiographically verified coronary artery disease. Blood pressure at rest, plasma renin activity, and plasma concentration of atrial natriuretic peptide were measured after treatment periods of two weeks. Bicycle exercise tests at the same time should evaluate ST-segment depression at comparable maximal workload, work capacity, blood pressure, and heart rate at exercise. In comparison to placebo, benazepril reduced arterial blood pressure significantly from 140 +/- 14/90 +/- 11 mm Hg to 125 +/- 16/84 +/- 10 mm Hg (p less than 0.05) and increased plasma renin activity from 2.19 +/- 3.76 ng/ml/h to 9.62 +/- 8.49 ng/ml/h (p less than 0.005). In contrast, ST-segment depression decreased only slightly and not significantly from 2.09 +/- 1.22 mm to 1.91 +/- 1.00 mm. Benazepril had neither an effect on the frequency of episodes of angina pectoris nor did it reduce the amount of GTN-consumption. Also, work capacity and plasma concentration of atrial natriuretic peptide were not changed in comparison to placebo. Although the significant reduction of blood pressure and the highly significant increase of plasma renin activity demonstrate the specific action of benazepril, a significant anti-ischaemic effect could not be established.
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PMID:[Treatment of chronic stable angina pectoris with angiotensin converting enzyme inhibition--a randomized, placebo-controlled, double-blind cross-over study]. 192 85

To assess the anti-anginal and anti-ischaemic efficacy of the ACE-inhibitor enalapril in normotensive coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Eight male patients, aged 45-68 years, with stable effort angina were given enalapril (10 mg) once a day or placebo for 7 days. Maximal exercise stress tests 10w/min in the upright position were performed at the end of each period. In comparison to placebo, enalapril increased significantly 1 mm of ST depression time and decreased significantly ST depression at maximal common work. Moreover, enalapril increased significantly the angina threshold and exercise duration. Three of the eight patients ended the exercise without pain. The rate-pressure product was not significantly modified at any time. Thus, the anti-ischaemic and anti-anginal activity may be due to an increase of coronary blood flow, rather than a reduction of MVO2 consumption.
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PMID:Effects of enalapril in normotensive patients with stable effort angina: a double blind, placebo controlled study. 208 65

We investigated the acute effect of the new long-acting ACE-inhibitor ramipril on angina-limited exercise tolerance and exercise-induced ST-depression in 18 normotensive patients with angiographically confirmed coronary artery disease in a double-blind, placebo-controlled study. Patients underwent a repeat exercise ECG 24 hours following either 5 mg ramipril p.o. or placebo. Plasma-ACE activity (nmol/min x ml) in the ramipril-group (n = 8) was significantly reduced 24 hours after 5 mg ramipril compared to placebo (n = 10): 14.0 +/- 2.0 vs 87.2 +/- 13.5, p less than 0.001. Exercise-induced ST-segment depression was not different before and after ramipril or placebo. Heart rate at rest and during angina-limited exercise was not different between the first exercise-ECG and that after ramipril or placebo, nor between the groups. Systolic arterial pressure (mmHg) was slightly, but insignificantly, lower after than before ramipril at rest (113.8 +/- 5 vs 125 +/- 6.8) and at maximal exercise, 1.5 watt/kg (150 +/- 9.4 vs 158.3 +/- 13.3). In the placebo group, blood pressure at rest and during exercise was not different before and after placebo: 126 +/- 4.7 vs 125.5 +/- 7.5 and 157.5 +/- 3.8 vs 158 +/- 3.6. Rate-pressure-product (mmHg/min x 1000) at rest prior to (8.42 +/- 0.83 and 8.95 +/- 0.51) and after ramipril or placebo (8.00 +/- 0.94 and 8.93 +/- 0.71) showed no significant difference. Similarly, rate-pressure-product at maximal exercise was equal among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute effects of the angiotensin converting enzyme inhibitor ramipril in patients with coronary heart disease]. 213 4

The anti-anginal effect of the ACE inhibitor enalapril, at a dosage of 5 mg twice a day, was tested in a randomised, placebo-controlled double-blind trial on 12 normotensive patients with proven coronary-heart disease. There was a reduction of exercise-induced ST depression by 22% already after the first dose of 5 mg. After 15 days of treatment the ST depression had decreased by 35% (P less than 0.05).
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PMID:[Anti-ischemia effect of enalapril in coronary heart disease. A randomized placebo-controlled double-blind study]. 283 91

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.
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PMID:Angiotensin converting enzyme inhibitors. II. Clinical use. 305 46

Serum angiotensin-converting enzyme activity (s-ACE) was measured spectrophotometrically in a variety of renal disorders. In 111 renal patients not on dialysis, s-ACE was slightly lower (22.9 +/- 5.9 U/ml; mean +/- SD) than in 116 controls 24.4 +/- 6.2 U/ml). In 52 patients on chronic hemodialysis s-ACE was 24.1 +/- 4.7 U/ml; serial analyses done before initiation of chronic dialysis showed a significant increase in s-ACE levels towards normal values. In 38 renal allograft recipients s-ACE was relatively low (22.0 +/- 5.0 U/ml); a significant decrease in s-ACE was observed in patients followed from the time of transplantation (24.6 +/- 6.4 U/ml) to two weeks after transplantation (20.2 +/- 4.5 U/ml). S-ACE was also depressed (17.4 +/- 2.6 U/ml) in 12 patients with acute renal failure, and it increased in parallel with normalization of renal function. S-ACE was normal (24.4 +/- 5.7 U/ml) in 14 patients with essential hypertension. Elevated s-ACE (above mean of controls + 2 SD) was observed in only one patient of the total series. We could not confirm previous reports on elevated s-ACE in dialysis patients, but several factors invalidate a direct comparison between series. Thus, the deviations in s-ACE in renal disorders seem to be discrete: depressed levels in acute renal failure and a relative depression in undialyzed patients with chronic renal disorders. The low activity after transplantation may be secondary to the immunosuppressive treatment.
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PMID:Angiotensin-converting enzyme activity in renal disorders: influence of disease pattern, hemodialysis and transplantation. 632 76


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