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 extravasation of plasma proteins and formation of interendothelial gaps in submucosal microvessels by mucosally-applied bradykinin (BK), were studied in the rat trachea. The effects of topical and systemic (s.c.) glucocorticoid budesonide (BUD) were investigated in the presence or absence of inhibitors of BK-degradtive enzymes (captopril and thiorphan 10 microM to inhibit angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), respectively). Inhibition of these enzymes markedly increased the inflammatory responses to BK. Topical BUD (3 microM, 10 min contact, 90 min before BK) significantly decreased the volume of plasma in the tracheal lumen, both in the absence and presence of the enzyme inhibitors. Thus, the main anti-transudation mechanism of topical BUD is not related to modulation of BK-breakdown. However, this may be the mechanism for systemic BUD. Neither topical nor systemic BUD prevented interendothelial gap formation.
Agents Actions 1991 Sep
PMID:Attenuation of bradykinin-induced mucosal inflammation by topical budesonide in rat trachea. 179 30

Pretreatment with captopril, a kininase II inhibitor, at 10 mg/kg i.p. or s.c., significantly increased the writhing response induced by a minimum effective dose (0.75 mg/kg i.p.) of phenylbenzoquinone (PBQ), by 91-148%. 1,10-Phenanthroline, a carboxypeptidase B inhibitor (2 mg/kg i.p.), in combination with captopril enhanced the algesic effect of PBQ by 309-360%. Captopril also doubled the number of writhes induced by a minimum effective dose of BK (5 micrograms/kg i.p.) in PGE2-pretreated mice. The writhing responses induced by higher doses of PBQ or BK were not affected by these inhibitors. The hyperalgesic effect of BK (1 micrograms) injected into the hindpaw of rats was significantly increased and prolonged by coinjection of captopril (30 micrograms) and 1,10-phenanthroline (30 micrograms) and was prevented by carboxypeptidase B (1 mg). These data indicate that BK plays a role in pain in these models, a role which appears of greatest relevance at threshold algesic stimulation.
Agents Actions 1991 Sep
PMID:Evidence for a role of bradykinin in experimental pain models. 179 37

Early treatment of patients with myocardial infarction and left ventricular dysfunction was performed in 90 patients aiming at influencing left ventricular remodelling. After twelve months of treatment with 25 mg captopril t.i.d. left ventricular ejection fraction was improved by 10% in comparison to a treatment with 40 mg of frusemide or placebo (p = 0.001). Late treatment of the patients not treated with captopril resulted in partial reversal of left ventricular dilatation, while withdrawal of captopril therapy in stable patients with ejection fractions over 30% and without clinical signs of congestive heart failure did not result in deterioration of left ventricular function. These results give a sound rationale for the earlier use of ACE-inhibitors in the treatment of congestive heart failure and left ventricular dysfunction.
Herz 1991 Sep
PMID:Studies of left ventricular dysfunction following myocardial infarction. 182 Feb 93

The impact of treatment on prognosis of patients with chronic congestive heart failure depends not only on pharmacological therapy but also on nonpharmacological aspects of patient management. Patient compliance, life style changes, salt and fluid restriction, detailed patient information and measures of self control greatly affect therapeutic efficacy. Reasons for hospitalizations and emergency room visits: In an analysis of 82 admissions of patients for decompensated chronic congestive heart failure we found poor compliance with drug treatments or dietary instructions as causally related factors in 30 patients, uncontrolled hypertension in 22 patients, acute infection in 18 and acute myocardial ischemia in 18 patients. More than half of the patients had weight gain before decompensation, that had not been adequately answered by changes in medication. Inadequate patient information: Inadequate knowledge about necessary life style changes at the time of hospital discharge is often found in patients with chronic heart failure. Less than 50% of these patients remembered correctly the instructions on key issues of necessary life style changes and diet. Drug treatment of heart failure: Recent controlled drug trials have not gained enough weight in therapeutic decisions of physicians treating heart failure patients. While ACE-inhibitors have been shown to improve longevity in congestive heart failure only 6% of patients with heart failure are treated with these drugs, while 5% are treated with calcium antagonists which have not been proven to be of symptomatic or prognostic benefit and may be harmful as well in this disease. Inadequate dosage in patients with chronic renal failure or in elderly patients as well as inadequate choice of drugs lead to side effects in a considerable percentage of patients.
Herz 1991 Sep
PMID:[Effects of patient information, compliance and medical control on prognosis in chronic heart failure]. 182 Feb 95

Vasodilators have been shown to improve hemodynamics of the failing heart as a short-term effect and to decrease mortality as a long-term result. We therefore studied the effect of different vasodilators on myocardial mechanics and energetics in patients with idiopathic dilated cardiomyopathy (IDC) NYHA II to III. In these patients undergoing routine heart catheterization myocardial oxygen consumption was measured using the argon method, and left ventricular pressure and geometry were obtained from left ventricular angiography using a Millar tip microcatheter. All data were analyzed for one single heart beat. The best correlation was found between MVO2/beat and the systolic stress-time integral which considers left ventricular pressure, wall thickness, and geometry. The relation between MVO2/beat and peak systolic wall stress was less relevant. No correlation was found between MVO2/beat and pressure-volume work, dP/dtmax, and mean velocity of circumferential fiber shortening. The intravenous application of nitroprusside and the ACE-inhibitor benazepril decreased both the systolic stress-time integral and the myocardial oxygen consumption in proportion to each other indicating unchanged economy of myocardial contraction. In contrast to other vasodilators, beta 1-agonists and phosphodiesterase inhibitors increase myocardial oxygen consumption independently of changes in the stress-time integral. In conclusion, vasodilators decrease left ventricular pressure and chamber size and thereby proportionally reduce MVO2/beat. The reduction of energy needed for myocardial contraction may partially explain the long-term effects of the ACE-inhibitors and combinations of vasodilators. Pure positive inotropic substances, especially beta 1-agonists, increase myocardial oxygen consumption with minor changes of systolic stress-time integral.(ABSTRACT TRUNCATED AT 250 WORDS)
Herz 1991 Sep
PMID:Left ventricular geometry, myocardial function and energetics of the dilated left ventricle. Influence of vasodilators and positive inotropic substances. 182 Feb 96

Progression of heart failure ("expected mortality") and sudden cardiac death ("unexpected mortality"), presumably secondary to ventricular arrhythmia, are the major causes for the poor prognosis in chronic heart failure (CHF). Limitations of this classification ultimately stem from inaccuracies in establishing the mechanism of death at the time of death. Elucidation of the determinants of patients prone to sudden death and the effects of treatment modalities on the rate of sudden death remain hidden. Unexpected mortality is probably secondary to arrhythmic death but denotes only that death occurred within some brief interval (arbitrarily less than one hour in most studies) and does not exclude other causes. The demonstrated benefit of ACE inhibitors for improving total mortality as illustrated by the findings of the VHeFT, Captopril Multicenter and CONSENSUS, and the improved event-free survival shown by Munich Mild Heart Failure Trial for low-dose captopril argues strongly for their use in patients with CHF. These agents are confirmed to reduce the risk of death from pump failure; the effects on sudden death are less clear. Although many favorable effects contribute to improved hemodynamics, neuroendocrine and electrolyte status as discussed, at present, it is not possible to predict the precise mechanism by which these agents extend life and whether they reduce the frequency of "sudden" deaths.
Herz 1991 Sep
PMID:Can angiotensin converting enzyme (ACE) inhibitors influence the risk of sudden cardiac death in patients with heart failure? 182 Feb 99

Regression of LVH is a reasonable adjunctive goal of blood pressure treatment, given the well described risks of hypertrophy and the possible benefits inherent in its reversal. Data suggest that any of the presently recommended agents for initial monotherapy, i.e. diuretics, beta adrenergic inhibitors, ACE inhibitors, or calcium blockers, are effective in achieving regression of hypertrophy if blood pressure lowering is achieved. While there may be other factors that play a role in the genesis and maintenance of cardiac hypertrophy in the hypertensive subject, it would appear that blood pressure elevation is probably the most important one. If reduction of blood pressure to normotensive levels can be achieved and maintained by the use of any of the antihypertensive agents (including the vasodilators, if used in combination with adrenergic inhibitors and/or diuretics), there is a reasonable chance that cardiac hypertrophy can be prevented or reversed and prognosis improved.
Eur Heart J 1991 Sep
PMID:Antihypertensive drug therapy and regression of left ventricular hypertrophy: a review with a focus on diuretics. 183 64

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.
Clin Cardiol 1991 Sep
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

Progressive enlargement following myocardial infarction can be anticipated to adversely effect outcome since prognosis is intimately related to the degree of left ventricular dysfunction and resultant ventricular cavity size. Recent experimental and clinical data have indicated that chronic angiotensin converting enzyme inhibitor therapy can be effective in attenuating the ventricular enlargement which occurs following infarction. These observations have provided a rationale for ongoing large multicenter clinical trials designed to determine whether angiotensin converting enzyme inhibition will be of clinical benefit following infarction. This article reviews the rationale for studies of angiotensin converting enzyme inhibition in post-infarct patients and summarizes the ongoing international research effort to fully define the role of angiotensin converting enzyme inhibition following infarction.
Herz 1991 Sep
PMID:Angiotensin converting enzyme inhibition therapy following myocardial infarction. Rationale for clinical trials. 184 Feb 97

From the lysosomal cysteine proteinase cathepsin B, isolated from human liver in its two-chain form, monoclinic crystals were obtained which contain two molecules per asymmetric unit. The molecular structure was solved by a combination of Patterson search and heavy atom replacement methods (simultaneously with rat cathepsin B) and refined to a crystallographic R value of 0.164 using X-ray data to 2.15 A resolution. The overall folding pattern of cathepsin B and the arrangement of the active site residues are similar to the related cysteine proteinases papain, actinidin and calotropin DI. 166 alpha-carbon atoms out of 248 defined cathepsin B residues are topologically equivalent (with an r.m.s. deviation of 1.04 A) with alpha-carbon atoms of papain. However, several large insertion loops are accommodated on the molecular surface and modify its properties. The disulphide connectivities recently determined for bovine cathepsin B by chemical means were shown to be correct. Some of the primed subsites are occluded by a novel insertion loop, which seems to favour binding of peptide substrates with two residues carboxy-terminal to the scissile peptide bond; two histidine residues (His110 and His111) in this "occluding loop' provide positively charged anchors for the C-terminal carboxylate group of such polypeptide substrates. These structural features explain the well-known dipeptidyl carboxypeptidase activity of cathepsin B. The other subsites adjacent to the reactive site Cys29 are relatively similar to papain; Glu245 in the S2 subsite favours basic P2-side chains. The above mentioned histidine residues, but also the buried Glu171 might represent the group with a pKa of approximately 5.5 near the active site, which governs endo- and exopeptidase activity. The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes.
EMBO J 1991 Sep
PMID:The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. 186 26


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