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 report here the protective effect of the angiotensin converting enzyme inhibitors captopril and ramiprilat against damage due to oxygen free radicals on aortic endothelium in a superfusion cascade system. Oxygen free radicals were generated by electrolysis of Krebs solution. Acetylcholine was infused through the donor aortic segment and relaxation of the detector aortic ring was used to indicate the release of endothelium-derived relaxing factor (EDRF). The percentage of relaxation before and after electrolysis was compared to calculate the relaxation index. Electrolyzed Krebs solution impaired the release of EDRF, as shown by a reduction in the relaxation index with a concomitant decrease in the tissue levels of superoxide dismutase and 6-keto PGF1 alpha and increase in malondialdehyde in the donor vessel. Captopril (100 microM), 15 microM ramiprilat and 30 nM iloprost had a protective effect as shown by a significantly smaller reduction in the relaxation index and the level of 6-keto PGF1 alpha and by an attenuation of the production of malondialdehyde. In addition, 1 microM indomethacin almost eliminated the protection by captopril. We conclude that both the SH-containing angiotensin-converting enzyme inhibitor captopril and the non-SH-containing ramiprilat, as well as iloprost, a stable analog of prostacyclin, can protect rabbit aortic endothelium against damage due to oxygen free radicals. The mechanism of such protection may be partly associated with the facilitation of the release of prostacyclin and consequent reduction in lipid peroxidation.
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PMID:Prostacyclin-mediated protection by angiotensin-converting enzyme inhibitors against injury of aortic endothelium by free radicals. 137 80

Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p less than .05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilities. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.
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PMID:Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors. 138 99

If the failing left ventricle could be given an effective push, other approaches to the treatment of heart failure would not be needed. We have inotropes only for short-term parenteral use. We have no safe inotrope for chronic oral use. The effect of digitalis is only feeble and the phosphodiesterase inhibitors seem to increase mortality from sudden death. Diuretics are dramatic for acute pulmonary oedema and the mainstay for chronic fluid retention but do not improve the pump and by reducing blood volume stimulate the renin angiotensin system to vasoconstriction, further fluid retention and hypokalaemia. Nitrates drop pre-load without reducing blood volume but tolerance is a problem and stroke volume does not increase. Reduction of afterload helps the failing ventricle to empty, the pull and output increases. The angiotensin converting enzyme inhibitors (ACEI) are now the cornerstone of heart failure treatment, reducing mortality in severe heart failure (CONSENSUS) and superior to standard vasodilator therapy (V-HeFT-2) at improving the survival of patients with mild to moderate heart failure. ACEI can reduce the incidence of ventricular ectopy and probably do this through improving left ventricular function, from decreasing sympathetic tone, reducing myocardial oxygen demand or increasing serum potassium but ACEI did not diminish the incidence of sudden death in the SOLVD trial despite reducing mortality. Disappointingly little improvement in exercise tolerance and persistence of chronic fatigue in heart failure concentrated attention on the periphery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The push, the pull and the periphery. 144 45

1. Captopril was evaluated as an adjuvant to diuretic and digoxin therapy in heart failure in old age, using walking ability, minute ventilation and oxygen consumption and plasma atrial natriuretic factor (ANF) concentration as measures of outcome. 2. Twenty patients, mean (s.d.) age 81 (6) years, entered a double-blind, randomised, crossover study of three treatments, a twice daily regimen of captopril (AA), at a dosage established by titration against serum angiotensin converting enzyme (ACE) activity, the same dosage in the morning with placebo at night (AP), and twice daily placebo (PP). Each treatment lasted 3 weeks. A 2 week run-in period on triple therapy, with AA captopril, was used to assess stability and compliance. Seventeen completed all treatments: three completed two. 3. Any benefit of captopril was modest and there was deterioration in gait on the titrated dosage 3 months afterwards (P = 0.04). Efficacy in the old may be greatest when the titrated dose (25 or 50 mg) is given once daily: the multiple daily doses recommended may be unnecessarily demanding. 4. Walking performance was measured by gait analysis (GA) at free walking speed and by a simple walking test (SWT), in which patients stopped at the first relevant symptom. There was a consistent tendency for four measures of performance (GA: speed, stride length and double support time; SWT distance) to be best on the AP treatment, next best on AA, and worst on PP but for the fifth, SWT speed, AP and AA were similar. The trend appeared most marked for SWT distance, mean (s.e. mean) values for AP, AA and PP being 123 (15), 94 (16) and 75 (16) m, respectively. However, the treatment effect did not reach statistical significance at the 0.05 level. 5. There was no significant difference between treatments in minute ventilation, minute oxygen consumption, or their ratio, either at rest or on exercise. 6. Resting ANF concentrations were nearly four times higher (P = 0.0001) in the patients than those, mean (s.e. mean) 66 (5) pmol l-1, in eleven healthy volunteers of mean age 80 (6) years, and the increase on exercise, seen in the controls (P less than 0.01), was absent. In the patients the resting plasma ANF concentration was significantly affected by treatment (P = 0.03), being less on both AP, 245 (9), and AA, 214 (9) than on PP, 264 (10) pmol l-1 (P = 0.02 and 0.03, respectively). 7. Baseline serum ACE activity was induced on active treatment. The change in ACE activity at 3 h post an active dose was significantly greater on AP than AA (P = 0.005). The increased sensitivity to inhibition during once daily administration was reflected in mean arterial pressure. The pre-dose standing pressure was less on AP than on PP (P less than 0.05), and the change in postural fall (pre-dose minus 2 h post), was greater (P = 0.004), but AA and PP were similar in these respects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of captopril on functional, physiological and biochemical outcome criteria in aged heart failure patients. 153 21

The aim of the study was to investigate whether oxygen causes a further decrease in pulmonary artery pressure after administration of calcium channel blocker-verapamil-or angiotensin converting enzyme inhibitor-captopril-in the secondary pulmonary hypertension. We studied 37 patients with the secondary pulmonary hypertension (mean pulmonary artery systolic pressure = 56.1 mm Hg) due to mitral stenosis. After having completed hemodynamic diagnostic procedures, basal oxygen test was performed and pulmonary artery pressure was recorded at 10 min of oxygen breathing. Then, 10 mg of verapamil was injected into the pulmonary artery of 16 patients and 21 patients received 75 mg of oral captopril. At the peak of vasodilation, 30 min after verapamil and 90 min after captopril administration, pulmonary artery pressure was recorded and oxygen test was repeated. Baseline oxygen test produced a statistically significant decrease in pulmonary artery pressure. Verapamil and captopril also lowered pulmonary artery systolic and diastolic pressures. The second oxygen test did not cause a further decrease in the pulmonary artery pressure; mean pulmonary artery systolic pressure was 52.3 +/- 23.7 mm Hg, pulmonary artery diastolic pressure 22.7 +/- 10.6 mm Hg before and 49.1 +/- 23.8 mm Hg and 23.0 +/- 13.5 mm Hg, respectively after the test in verapamil group, and 47.0 +/- 15.5 mm Hg and 21.7 +/- 8.4 mm Hg before and 46.6 +/- 15.4 mm Hg, respectively in captopril subset. The results may support the thesis that vasodilating effect depends rather on the degree of pulmonary vascular changes than on the vasodilatory mechanism of particular drugs.
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PMID:[Lack of additional action of oxygen on pulmonary artery pressure at the peak of verapamil or captopril action in pulmonary hypertension secondary to mitral stenosis]. 166 76

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.
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PMID:Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure. 168 43

Congestive heart failure (CHF) is a complex clinical syndrome affecting 1% of the U.S. population. The basic dysfunction, a lack of sufficient blood flow to the periphery, triggers reflex neurohumoral mechanisms that cause systemic vasoconstriction and sodium and water retention as the body attempts to protect vital organs. This, in turn, results in additional work for the failing heart and further deterioration. Vasodilators, in general, and angiotensin converting enzyme (ACE) inhibitors, in particular, interrupt this pathophysiology and improve hemodynamics. Enalapril, a long-acting ACE inhibitor, has been demonstrated to improve New York Heart Association (NYHA) functional class, pulmonary capillary wedge pressure, cardiac index, maximum oxygen uptake, and exercise tolerance in CHF patients. Data from a recent trial provide evidence that a group of patients with severe CHF who were treated with enalapril showed reduced heart size, reduced need for other heart-failure medication, and reduced mortality.
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PMID:Enalapril in the treatment of congestive heart failure. 169 16

Chronic hypoxia is known to be associated with a thickening of the media of pulmonary arteries. The goal of the present study was to assess if cilazapril, a novel long-acting angiotensin converting enzyme (ACE) inhibitor, could prevent this thickening. For this purpose, three groups of rats were studied. One group was kept in normal room air. Two other groups were exposed to chronic hypoxia (inspired fraction of oxygen equal to 8% during 4 weeks). One group of hypoxic rats was treated with placebo and the other group received cilazapril (as food admixture of approximately 3 mg/kg/day). After 4 weeks, rats were anesthetized and pulmonary artery pressure and hematocrit measured. Then, the lungs were perfused and fixed and morphometry of the pulmonary arteries was performed. Hypoxia induced an increase in pulmonary artery pressure and hematocrit associated with a dramatic increase in the thickness of the media of the pulmonary arteries. Cilazapril completely prevented the thickening of the media of the pulmonary arteries but did not significantly decrease the pulmonary artery pressure or right ventricular weight.
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PMID:Effects of cilazapril, a novel angiotensin converting enzyme inhibitor, on the structure of pulmonary arteries of rats exposed to chronic hypoxia. 170 54

The synthesis of adenosine triphosphate (ATP) depends on the coordinated interaction of oxygen delivery and glucose breakdown in the Krebs cycle. Cellular oxygen depots are non-existent, therefore the peripheral cells are totally dependent on the circulation for sufficient oxygen delivery. Shock is the clinical manifestation of cellular oxygen craving. The commonly measured variables--blood pressure, heart rate, urinary output, cardiac output and systemic vascular resistance--are not sensitive or accurate enough to warn of impending death in acutely ill patients nor are they appropriate for monitoring therapy. Calculated oxygen transport and oxygen consumption parameters provide the best available measures of functional adequacy of both circulation and metabolism. In order to optimise oxygen delivery (DO2), 4 interacting factors must be taken into account: cardiac output, blood haemoglobin content, haemoglobin oxygen saturation and avidity of oxygen binding to haemoglobin. For viscosity reasons, the optimal haemoglobin concentration is in the vicinity of 90 to 100 g/L, but for optimising the oxygen transport 100 to 115 g/L or a haematocrit of 30 to 35% seems better. The p50 (the pO2 at which haemoglobin is 50% saturated) describes the oxygen-haemoglobin dissociation curve; normally its value is +/- 27 mm Hg. It can be influenced by attaining normal body temperature, pH, pCO2 and serum phosphorous levels. In order to obtain an arterial blood saturation (SaO2) of more than 90% with acceptable haemodynamics, the ventilation mode and inspired oxygen fraction (FiO2) must be adapted; care must be taken not to stress the labile circulation with haemodynamic compromising ventilation techniques [e.g. high positive end expiratory pressure (PEEP) levels, inverse-ratio ventilation, etc.]. The factor most amenable to manipulation is the cardiac output, with its 4 determinants--preload, afterload, contractility and heart rate. In daily clinical practice, heart rate should be between 80 and 120 beats/min; small variations are acceptable. Important deviations must be treated by chemically [isoprenaline (isoproterenol)] or electrically (pacing techniques) accelerating the heart, or with the different antiarrhythmic drugs. A wide variety of agents is available to decrease the preload: diuretics [especially furosemide (frusemide)], venodilators like nitroglycerin (glyceryl trinitrate), isosorbide dinitrate (sorbide nitrate) and sodium nitroprusside, ACE inhibitors, phlebotomy, and haemofiltration techniques (peritoneal or haemodialysis, continuous arteriovenous haemofiltration). To increase the preload, volume loading using a rigid protocol ('rule of 7 and 3'), preferably with colloids, or vasopressor agents [norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine] are useful. Arterial vasopressors are needed to improve perfusion pressure of 'critical' (coronary and cerebral) arteries. Afterload can be decreased by arterial vasodilators. Predominantly arterial dilators are hydralazine and clonidine, while sodium nitroprusside, nitroglycerin and isosorbide dinitrate have combined arterial and venous dilating actions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Haemodynamic monitoring. Problems, pitfalls and practical solutions. 171 63

Uterine renin may regulate uteroplacental blood flow locally through changes in vascular resistance or systemically by supporting arterial blood pressure. Captopril (5 mg/kg) was given i.v. to 14 conscious pregnant rabbits at day 27.5 +/- 0.3 of gestation for the purpose of investigating the effects of angiotensin converting enzyme inhibition on uteroplacental blood flow and oxygen consumption. Control measurements (mean +/- S.E.M.) were compared to measurements made at 1 hr (n = 14) and at 3 to 4 hr (n = 7). Arterial blood pressure decreased from 80 +/- 3 to 66 +/- 3 mm Hg, P less than .01, and then declined further to 56 +/- 4 mm Hg, P less than .01. Cardiac output was unchanged at 1 hr, 799 +/- 79 vs. 705 +/- 61 ml/min, but was decreased to 634 +/- 29 ml/min by 3 to 4 hr, P less than .01. There was no change in renal blood flow from 102 +/- 13 ml/min. Total uterine blood flow decreased from 37 +/- 5 to 29 +/- 5 ml/min, P less than .01, and then to 23 +/- 1 ml/min, P less than .01, whereas placental blood flow decreased from 25 +/- 4 to 19 +/- 3 to 15 +/- 3 ml/min, P less than .01; there was no significant change in myoendometrial flow. Oxygen delivery per uterine horn decreased from 2.4 +/- 0.3 to 1.8 +/- 0.4 to 1.6 +/- 0.2 ml/min, P less than .005. Oxygen consumption per horn decreased from 1.31 +/- 0.14 to 1.05 +/- 0.15 ml/min by 1 hr, P less than .05, and there was no further decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of captopril on blood pressure, placental blood flow and uterine oxygen consumption in pregnant rabbits. 173 Oct 44


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