ACE inhibitors are becoming an important part of treatment in patients after acute myocardial infarction if they suffer from asymptomatic dysfunction of the left ventricle (ejection fraction of the left ventricle evaluated by echocardiography or isotope ventriculography 40% or less). It prevents the development of cardiac dilatation, it retards progression of the disease and the development of cardiac failure and reduces the necessity of hospitalization in patients with chronic cardiac failure (stage NYHA II-IV). ACE inhibitors are the drug of choice as they reduce significantly the general mortality of these patients. Treatment should not be initiated in the acute stage but after several days have elapsed after infarction, unless contraindications of treatment are present. Extensive investigations made during the past two years revealed moreover that ACE inhibitors effectively prevent also relapses of myocardial infarction or the development of unstable angina pectoris. Prevention of coronary attacks is most probably due to several effects of ACE inhibitors: a) reduction of blood pressure, b) coronary vasodilatation, c) the antiproliferative action of ACE inhibitors on vascular musculature, d) prevention of progression of atherosclerosis, e) prevention of myocardial hypertrophy, f) the favourable effect on endothelial function. So far we indicate for treatment with ACE inhibitors only patients after acute myocardial infarction with left ventricular dysfunction. Only subsequent research will show whether treatment with ACE inhibitors is of value in patients with preserved left ventricular function.

• MeSH
• Hemodynamics drug effects   MeSH
• Myocardial Infarction complications   physiopathology   prevention & control   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Humans MeSH
• Heart Failure drug therapy   prevention & control   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Angiotensin-Converting Enzyme Inhibitors MeSH

The reduction in overall mortality, cardiovascular mortality and the occurrence of myocardial infarction in patients treated with AT1 blockers is comparable with the use of ACE inhibitors. In addition, there is a lower proportion of AT1 blockers withdrawal of treatment due to adverse reactions.Key words: ACE inhibitors - AT1 blockers - cardioprotection - hypertension - renin-angiotensin-aldosteron system.

• MeSH
• Angiotensin II Type 1 Receptor Blockers adverse effects   therapeutic use   MeSH
• Hypertension drug therapy   MeSH
• Myocardial Infarction epidemiology   MeSH
• Angiotensin-Converting Enzyme Inhibitors adverse effects   therapeutic use   MeSH
• Cardiovascular Diseases drug therapy   mortality   MeSH
• Humans MeSH
• Renin-Angiotensin System MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Angiotensin II Type 1 Receptor Blockers MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH

BACKGROUND: The Angiotensin-I converting enzyme (ACE) is one of the most important components of the renin-angiotensin-aldosterone system controlling blood pressure and renal functions. Inhibitors of ACE are first line therapeutics used in the treatment of hypertension and related cardiovascular diseases. Somatic ACE consists of two homologous catalytic domains, the C- and N-domains. Recent findings have shown that although both domains are highly homologous in structure, they may have different physiological functions. The C-domain is primarily involved in the control of blood pressure, in contrast to the N-domain that is engaged in the regulation of hematopoietic stem cell proliferation. The currently available ACE inhibitors have some adverse effects that can be attributed to the non-selective inhibition of both domains. In addition, specific Ndomain inhibitors have emerged as potential antifibrotic drugs. Therefore, ACE is still an important drug target for the development of novel domain-selective drugs not only for the cardiovascular system but also for other systems. OBJECTIVE: Detailed structural information about interactions in the protein-ligand complex is crucial for rational drug design. This review highlights the structural information available from crystallographic data which is essential for the development of domain selective inhibitors of ACE. METHODS: Over eighty crystal complexes of ACE are placed into the Protein Database. An overview of X-ray ACE complexes with various inhibitors in C- and N-domains and an analysis of their binding mode have given mechanistic explanation of the structural determinants of selective ligand binding. In addition, ACE domain selective inhibitors with dual modes of action in complexes with ACE are also discussed. CONCLUSION: Selectivity of ACE inhibitors for the N- and C-domain is controlled by subtle differences in the amino-acids forming the active site. Reported studies of crystal complexes of inhibitors in the C- and N-domains revealed that most selective inhibitors interact with non-conserved amino-acids between domains and have distinct interactions with the residues in the S2 and S2' subsites of the ACE catalytic site. Moreover, unusual binding of the second molecule of inhibitors in the binding cavity opens new possibilities of exploiting more distant regions of the catalytic center in structure-based design of novel drugs.

• Keywords
• Angiotensin converting enzyme (ACE), C-domain, N-domain, crystal structure, non-prime binding, selective inhibitor.,
• MeSH
• Peptidyl-Dipeptidase A chemistry   metabolism   MeSH
• Angiotensin-Converting Enzyme Inhibitors chemistry   metabolism   MeSH
• Catalytic Domain MeSH
• Crystallography, X-Ray MeSH
• Humans MeSH
• Protein Domains MeSH
• Drug Design MeSH
• Substrate Specificity MeSH
• Protein Binding MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Peptidyl-Dipeptidase A MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH

ACE inhibitors, which till recently were used almost exclusively for treatment of cardiovascular diseases, are becoming a perspective group of drugs also in the treatment of nephropathies. It was found that they are effective in particular in the treatment of proteinuria of varying origin and have also a marked renoprotective effect and are therefore recommended to retard progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard progression of chronic glomerulonephritis and diabetic nephropathy. We may expect already in the near future that their therapeutic application will be substantially extended also in clinical nephrology.

• MeSH
• Angiotensin-Converting Enzyme Inhibitors adverse effects   therapeutic use   MeSH
• Humans MeSH
• Kidney Diseases drug therapy   physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Angiotensin-Converting Enzyme Inhibitors MeSH

Morbidity and mortality resulting from cardiotoxic complications of anticancer therapy is still unacceptably high. Despite advances in the understanding of the pathomechanisms of cardiotoxicity, in prevention and detection of these complications, progressive ventricular dysfunction in cancer survivors represents a great therapeutic problem. Ventricular dysfunction is a life-threatening complication particularly in patients treated with anthracycline cytostatics. Anthracycline-induced loss of myocytes leads to an inadequate ventricular hypertrophy, which produces a rise in left ventricular (LV) afterload and deterioration of ventricular contractility culminating in heart failure. Efficacy of angiotensin-converting enzyme (ACE) inhibitors for the treatment of asymptomatic and symptomatic LV dysfunction in various clinical settings has been confirmed in a number of controlled, randomized trials. Until now, there are only few published data supporting the use of ACE inhibitors to treat patients with ventricular dysfunction-induced by anthracyclines. Cardio-protection with ACE inhibitors in children and adolescents treated with anthracyclines in contrast to ACE inhibition in adults after anthracycline therapy is a controversial topic. Evidence from the recent follow up study indicates a progressive deterioration of left ventricular wall thinning in childhood cancer survivors treated with enalapril. The ongoing large controlled, double blind, randomized trials will provide an important information concerning the efficacy of ACE inhibitors to prevent progression of ventricular dysfunction in paediatric oncologic patients.

• MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Anthracyclines adverse effects   therapeutic use   MeSH
• Ventricular Dysfunction, Left chemically induced   drug therapy   physiopathology   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Humans MeSH
• Heart drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Antineoplastic Agents MeSH
• Anthracyclines MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH

• MeSH
• Angiotensin-Converting Enzyme Inhibitors administration & dosage   MeSH
• Coronary Disease drug therapy   MeSH
• Humans MeSH
• Heart Failure drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH
• Names of Substances
• Angiotensin-Converting Enzyme Inhibitors MeSH

ACE inhibitors which till recently were used only in the treatment of cardiovascular diseases are becoming a perspective group of drugs also in the treatment of chronic nephropathies. It was revealed that they are effective in particular in the treatment of proteinuria of different etiology and have also a marked renoprotective effect and are therefore recommended to slow down the progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard the progression of chronic glomerulonephritis and diabetic nephropathy. It may be excepted that their therapeutic application will in the near future be extended also to clinical nephrology.

• MeSH
• Angiotensin-Converting Enzyme Inhibitors adverse effects   pharmacokinetics   therapeutic use   MeSH
• Humans MeSH
• Kidney Diseases drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Angiotensin-Converting Enzyme Inhibitors MeSH

Captopril, the classic inhibitor of the angiotensin converting enzyme, was employed in several large clinical studies in recent years. The effect of captopril was compared either with placebo, or captopril was selected as the reference ACE inhibitor for comparison with another therapy. In the classic study SAVE, captopril administered to patients after myocardial infarction with a dysfunction of the left chamber reduced mortality by 19%. Though in the study ELITE the AT1 blocker losartan was more effective to reduce mortality in patients with chronic heart failure than captopril, the larger and mortality-oriented study ELITE II did not demonstrate a difference in mortality reduction between captopril and losartan. ACE inhibitors thus remain drugs of choice in chronic heart failure. AT1 blockers are to be used in the cases when ACE inhibitors are not tolerated. The study CAPPP has demonstrated that captopril in hypertonic patients not only effectively decreases blood pressure but exerts a similar effect on mortality reduction as the classic treatment with a diuretic and a betablocker, the most effective being captopril in diabetic patients. Administration of captopril in hypertonic patients with diabetes mellitus in the study UKPDS had an effect on mortality reduction as well as micro- and macrovascular complications of diabetes similar to that of atenolol. The ongoing study VALIANT compares the AT1 blocker valsartan or a combination of valsartan and captopril with captopril alone on patients at risk after myocardial infarction. Also at the beginning of the 21st century captopril maintains a stable position in the treatment of the cardiovascular system.

• MeSH
• Antihypertensive Agents therapeutic use   MeSH
• Myocardial Infarction drug therapy   physiopathology   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Captopril therapeutic use   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Heart Failure drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antihypertensive Agents MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH
• Captopril MeSH

In a retrospective study a total of 44 ambulatory examinations were made before enalapril was administered to 13 patients with essential hypertension and 52 ambulatory examinations during enalapril treatment of these patients. All patients were followed up on a long-term basis: 1. without enalapril treatment (2-24 months), 2. during enalapril treatment (4-24 months). For both investigation periods arithmetic means of plasma creatinine were calculated. The length of the investigation period was intentionally used as the sole criterium for inclusion in the group of patients. In nine patients during treatment the serum creatinine levels rose. The authors found a close positive correlation between the rise of plasma creatinine levels and the patients' age (correlation coefficient r = 0.59, n = 13, p < or = 0.02). Between the rise of creatinine (dependent variable) and independent variables (daily enalapril dose, initial creatinine blood level, the drop of the median arterial pressure during enalapril treatment) no close relationships were found. The rise of creatinine during enalapril treatment can be explained by a drop of the filtration pressure in the glomeruli during dilatation of the vas efferens. This drop of the filtration pressure was manifested by a slight increase of plasma creatinine only in patients with a drop of the renal perfusion (haemodynamic) reserve, i.e. in more advanced age groups.

• MeSH
• Enalapril therapeutic use   MeSH
• Hypertension blood   drug therapy   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Creatinine blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Enalapril MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH
• Creatinine MeSH

• MeSH
• Hemodynamics drug effects   MeSH
• Angiotensin-Converting Enzyme Inhibitors * MeSH
• Captopril therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Heart Failure drug therapy   physiopathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Angiotensin-Converting Enzyme Inhibitors * MeSH
• Captopril MeSH