enalapril and Myocardial-Ischemia

Topics: Adrenergic beta-Antagonists; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Controlled Clinical Trials as Topic; Enalapril; Female; Humans; Hypertension; Indoles; Male; Middle Aged; Myocardial Ischemia; Nifedipine; Perindopril; Placebos; Risk Factors; Surveys and Questionnaires; Time Factors; Vasodilator Agents; Verapamil

Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Captopril; Cardiovascular Diseases; Enalapril; Heart Failure; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Renin-Angiotensin System; Ventricular Dysfunction

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aspirin; Case-Control Studies; Clinical Trials as Topic; Drug Interactions; Enalapril; Evidence-Based Medicine; Heart Failure; Hemodynamics; Models, Animal; Multicenter Studies as Topic; Myocardial Ischemia; Prostaglandin Antagonists; Prostaglandins; Pulmonary Circulation; Renal Circulation; Safety; Vasodilation; Vasodilator Agents

The causes of hypertensive microvascular ischemia are reviewed along with diagnostic factors. Stress/rest thallium-201 scintigraphy is shown to have a predictive value of 78% for a diagnosis of microvascular disease in hypertensive patients with exertional angina and left ventricular hypertrophy. Lack of isotope uptake at peak stress correlates well with the decrease in coronary flow reserve in ischemic segments, which is 2-3 times lower than in normal subjects. Treatment with enalapril produces regression of left ventricular hypertrophy, normalization of thallium-201 uptake, and an increase in exercise capacity in patients with microvascular angina.

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Coronary Circulation; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Microcirculation; Myocardial Ischemia; Radionuclide Imaging; Thallium Radioisotopes

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomegaly; Enalapril; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris-symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine to what extent under clinical conditions coronary flow reserve can be improved, in hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (Dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with the ACE-inhibitor enalapril (10-20 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, the coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a decrease in LV muscle mass by about 8%, coronary reserve was improved after enalapril by 48%. It is likely that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities at the level of the coronary microcirculation. Consequently, it seems that reparation of hypertensive remodeling of the coronary microcirculation can be induced by ACE-inhibitor therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Circulation; Enalapril; Humans; Hypertension; Microcirculation; Myocardial Ischemia

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Captopril; Drug Evaluation; Enalapril; Humans; Hypertension; Myocardial Ischemia

The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial.. Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy.. We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide.. Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11).. Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiomyopathy, Alcoholic; Cardiomyopathy, Dilated; Cardiotoxicity; Cardiovascular Diseases; Cause of Death; Dangerous Behavior; Diabetic Cardiomyopathies; Drug Combinations; Enalapril; Female; Heart Failure; Heart Valve Diseases; Hospitalization; Humans; Hypertension; Infections; Male; Middle Aged; Mortality; Myocardial Ischemia; Peripartum Period; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; Virus Diseases

Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown.. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy.. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function.

Topics: Adolescent; Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Infant, Newborn; Male; Myocardial Ischemia; Prospective Studies; Systole; Tetrazoles; Time Factors; Treatment Outcome; Valsartan; Ventricular Dysfunction, Left; Ventricular Function, Left

In various models, angiotensin-converting enzyme (ACE) inhibitors and K+(ATP) channel openers can potentiate and mimic ischaemic preconditioning, respectively. Our aim was to determine whether these characteristics are shared by the phenomenon of warm up in angina, often regarded as a surrogate of ischaemic preconditioning.. Twenty patients with ischaemic heart disease were assigned in a double blind, randomized cross-over design to equivalent pressor doses of nicorandil 20 mg bid, enalapril 10 mg bid, losartan 25 mg bid, or placebo for 3 days. Patients underwent three consecutive exercise tolerance tests on each medication separated by a 1-week interval. Each patient underwent 12 exercise tests in total and 13 patients completed the study. On each medication the second exercise was separated from the first by 15 min of rest and the third exercise was performed 90 min after the second to control for training. The time to 0.1 mV ST depression and rate pressure product at 0.1 mV ST depression increased significantly in all groups during exercise two compared with exercise one. Nicorandil reduced angina but did not attenuate this warm up effect. This benefit of first exercise waned by test three with placebo, losartan, and nicorandil, but not with enalapril.. In contrast to predictions based on ischaemic preconditioning the magnitude of the warm up was apparently unaltered by nicorandil, losartan, or enalapril, however its duration seemed to be extended by enalapril. Thus ischaemic preconditioning and warm up angina are likely to have differing pharmacological profiles suggesting a diverse underlying mechanism.

Topics: Adaptation, Physiological; Angina Pectoris; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cross-Over Studies; Double-Blind Method; Electrocardiography; Enalapril; Exercise Test; Female; Humans; Ischemic Preconditioning, Myocardial; Losartan; Male; Middle Aged; Myocardial Ischemia; Nicorandil; Potassium Channels; Regression Analysis; Vasodilator Agents

To elicit the role of endothelial dysfunction in development of cardiorenal syndrome in patients with diabetes mellitus type 1 (DM1) with diabetic nephropathy (DN) and to evaluate the efficacy of endotheliotropic drugs: nebivolol (a selective beta-blocker) and enalapril (ACE inhibitor).. The trial enrolled 60 patients with DM1: 15 patients with normoalbuminuria (NAU), 15 patients with microalbuminuria (MAU), 15 patients with proteinuria (PU) and 15 with chronic renal failure (CRF). The control group consisted of 15 healthy volunteers matched by sex and age. All the patients were examined for endothelium-dependent dilation of the brachial artery (by duplex scanning in the test with reactive hyperemia), serum markers of endothelial dysfunction (endothelin-1--ET-1), Willebrand factor (WF), inflammation markers (C-reactive protein-CRP), incidence rate of ischemic heart disease (IHD). 24-h arterial pressure monitoring and echocardiography were also made. For 12 weeks the patients were given nebivolol monotherapy in a dose 5 mg/day or enalapril monotherapy in a dose 10 mg/day. The effects of these drugs on urinary excretion of albumin and protein, arterial pressure, circadial rhythm of arterial pressure and endothelial dysfunction were studied.. In DM1 patients DN advances with an increase in development of IHD: in MAU--by 13%, PU--by 33%, CRF--53%. Concentric hypertrophy and left ventricular remodeling were registered in 33, 40 and 60% of cases, respectively. A circadian rhythm disturbance correlated with DN severity. DN progression was associated with increasing endothelial dysfunction. It is shown that nebivolol and enalapril correct endothelial dysfunction, have comparable antiproteinuric and antihypertensive actions at different stages of nephropathy.. A close correlation was found between DN progression and development of cardiovascular pathology in DM1 patients. This serves the basis of cardiorenal syndrome. These two pathologies are associated with vascular endothelial dysfunction which leads to disorders in vascular tonicity regulation.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Benzopyrans; Biomarkers; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Enalapril; Endothelium, Vascular; Ethanolamines; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Nebivolol; Syndrome

To compare hypotensive and antiischemic efficacy of enalapril combination with trimetazidine or placebo, effects on plasmic lipid spectrum and membrane-cell parameters of erythrocytes and platelets in hypertensive patients with ischemic heart disease (IHD) in the presence of metabolic disturbances.. A randomized placebo-controlled comparative trial included 64 patients (mean age 55.60 +/- 0.52 years) with hypertension stage I-III, IHD (stable effort angina FC II-III, obesity of the first-third degree, diabetes mellitus type 2. The patients were divided into two groups matched by gender, age, duration of the disease, office blood pressure (OBP), functional class (FC) of effort angina, body mass index, glucose levels in the blood. 43 patients of group 1 received enalapril and trimetazidine. 21 patients of group 2 were treated with enalapril and placebo. The efficacy of the treatment was assessed by changes in the 24-h profile of BP and ECG, blood lipid spectrum and membrane-cell parameters.. A significant fall was seen in systolic blood pressure of both groups patients. In group 1 there was an additional lowering of temporal index of systolic pressure, nocturnal diastolic, mean 24-h diastolic, mean 24-h blood pressure, double product of ischemic episodes, total cholesterol, dienic conjugates in platelets. Catalase activity in erythrocytes rose.. An antiischemic effect of the therapy in stabilization of blood pressure, normalization of plasmic lipids and lipoperoxidase in erythrocytic and platelet membranes under multidirectional correlations between clinical and biochemical parameters point to different mechanisms of ischemic correction in enalapril and trimetazidine.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Catalase; Comorbidity; Drug Therapy, Combination; Enalapril; Female; Humans; Hypercholesterolemia; Hypertension; Lipid Peroxidation; Male; Middle Aged; Myocardial Ischemia; Severity of Illness Index; Trimetazidine; Vasodilator Agents

To compare the impact of therapy with dialtiazem and enapril on myocardial ischemia, this randomized study included 25 patients with chronic obstructive bronchitis and myocardial ischemia. A comparative assessment of the results of therapy showed a uniform time course of changes in the parameters of Holter monitoring and bicycle ergometry (BEM). In a group of patients receiving dialthizem, there were reduces in the number of episodes of painful and silent ischemia by 66.6 and 72.2%, respectively; the duration of myocardial ischemia and the value of the maximum ST depression decreased by 47.4%. In patients receiving enalapril, the episodes of painful and silent ischemia became fewer by 55.9 and 63.6%, respectively; the duration of ischemia and the value of the maximum ST depression decreased by 46 and 43%, respectively.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bronchitis, Chronic; Calcium Channel Blockers; Cardiovascular Agents; Diltiazem; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Time Factors; Treatment Outcome

The authors investigated in a one-year multicentric open study the effect of enalapril (Enalapril Lachema-Pliva) in 653 patients with mild to moderate hypertension treated in ambulance of 128 general practitioners and specialists in internal medicine. The blood pressure was checked after 6 weeks during the first six months and every 3 months during the second six months. Normal levels of diastolic pressure were achieved in 576 (82%) patients, whereby a combination of antihypertensive drugs had to be used in 383 (59%) patients. Complete renal functions were assessed in 51 patients, microalbuminuria declined from 91.8+/- 37.8 to 72.1 +/- 13.1 mg/l (p < 0.001), glomerular filtration was not affected. Parameters of insulin sensitivity were assessed in 117 patients, the complete lipid spectrum in 253 patients. IRI declined from 12.29 +/- 5.40 to 11.57 +/- 5.42 (p = 0.06) and glycosylated haemoglobin from 6.98 +/- 2.39 to 6.69 +/- 1.97 (p = 0.03), which slows improved insulin sensitivity. Total-cholesterol, LDL-cholesterol and triglycerides decreased significantly and HDL increased (p < 0.001). The left ventricle mass declined significantly after treatment, using Dewereux's calculation, by 17.2 %. The left ventricular diastolic function was not affected by the treatment, however, the lef aulium and left ventricle diminished in volume.

Topics: Antihypertensive Agents; Blood Pressure; Diabetes Complications; Diabetes Mellitus; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia

The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK.. Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied.. Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS).. Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group.. Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.

Topics: Acetylcholine; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Bradykinin; Cardiac Catheterization; Chest Pain; Coronary Angiography; Coronary Circulation; Drug Synergism; Echocardiography, Doppler; Enalapril; Female; Fibrinolysis; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Papaverine; Tissue Plasminogen Activator; Vasodilator Agents

Left ventricular hypertrophy (LVH) in hypertensive subjects is associated with an increased prevalence of ventricular arrhythmias. To evaluate the effect of antihypertensive treatment on cardiac arrhythmias (CA) and transient episodes of myocardial ischemia (TEMI), we studied 46 hypertensive patients with LVH, divided into four groups randomly treated with enalapril, hydrochlorothiazide (HCTZ), atenolol, or verapamil (SR-V) for 6 months. Office blood pressure and office heart rate values were recorded, in basal conditions, after 1 and 6 months of treatment, and all patients underwent echocardiography, electrocardiographic Holter monitoring, and stress testing. All drugs significantly lowered blood pressure, whereas left ventricular mass index was reduced by atenolol, enalapril, and SR-V, but not by HCTZ. Treatment induced a significant reduction in the number of patients with supraventricular arrhythmias (35 v 15, P < .034, and 28 v 8, excluding patients treated with HCTZ, P < .008). The number of patients with ventricular arrhythmias was also reduced (32 v 16 considering all groups, P < .08, and 24 v 9, excluding patients treated with HCTZ, P < .04). The number of TEMI during Holter monitoring significantly decreased from 47 to 23 (P = .043) in all patients, and from 39 to 14 (P = .013) excluding patients treated with HCTZ. In all groups, irrespective of treatment, a reduction of blood pressure, heart rate, and systolic blood pressure/heart rate product measured by exercise stress test was observed. The present study shows that in hypertensive patients with LVH, antihypertensive treatment with atenolol, enalapril and SR-V reduces LVH and decreases the prevalence of CA and TEMI. Treatment with HCTZ during the 6-month study did not alter LVH and did not appear to reduce CA and TEMI.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Atenolol; Blood Pressure; Electrocardiography, Ambulatory; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome; Verapamil

Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure.. Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).. Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Cross-Over Studies; Enalapril; Female; Fibrinolysis; Heart Failure; Heart Rate; Hemodynamics; Humans; Losartan; Male; Myocardial Ischemia; Plasminogen Activator Inhibitor 1; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Single-Blind Method; Tissue Plasminogen Activator; Ventricular Dysfunction, Left

In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aspirin; Cardiomyopathy, Dilated; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Enalapril; Exercise Test; Heart Failure; Hemodynamics; Humans; Losartan; Male; Middle Aged; Myocardial Ischemia; Oxygen Consumption; Pulmonary Diffusing Capacity; Pulmonary Ventilation; Respiratory Mechanics

Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction.. PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 (P = .002) for all-cause mortality, 2.55 (P = .003) for cardiovascular mortality, 2.55 (P = .005) for hospitalization for heart failure, 1.88 (P = .002) for development of heart failure, 1.92 (P = .001) for ischemic events, and 2.59 (P = .005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events.. Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity.

Topics: Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Norepinephrine; Placebos; Predictive Value of Tests; Prognosis; Renin; Risk Factors; Survival Rate; Ventricular Dysfunction, Left

Fifteen patients with angiographic evidence of significant coronary artery disease, exertional myocardial ischemia, and positive dipyridamole echocardiographic test results at basal conditions and after 7 days of placebo treatment were prospectively studied to see whether captopril (containing sulfhydryl) and enalapril (nonsulfhydryl) modify myocardial ischemia induced by exercise testing and the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to captopril (150 mg/day in 3 separate doses) or enalapril (20 mg/day) for 1 week. At the end of this period each patient crossed over to the alternate regimen after a washout period of 7 days. Exercise stress testing and dipyridamole echocardiographic testing were repeated at the end of each treatment period. Neither captopril nor enalapril had a significantly greater anti-ischemic effect than placebo in any patient. Exercise duration, time to onset of ST-segment depression, maximal workload, degree of ST-segment depression, and rate-pressure product were not affected by either drug. Neither captopril nor enalapril improved dipyridamole-induced mechanical dysfunction or ST-segment depression.

Topics: Adult; Aged; Angina Pectoris; Captopril; Cross-Over Studies; Dipyridamole; Double-Blind Method; Echocardiography; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Treatment Failure

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomegaly; Enalapril; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Drug Combinations; Enalapril; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Ischemia

To investigate whether treatment initiated with an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) for patients with ischemic heart disease, hypertension, or diabetes causes a reduction in hemoglobin (Hb) levels.. This was a retrospective cohort analysis using the computerized database of a large health maintenance organization. Included were all adults with a first purchase of an ACE-I, an ARB, or a calcium channel blocker (CCB) between January 1, 2004, and December 31, 2009, defined as the index date. Measures of Hb levels before and 1 year after the index date were reviewed, and the change was calculated. All the analyses were stratified by pharmaceutical class. The main exposure variables were the proportion of days covered (PDC) by these drugs and the mean enalapril dosage (for enalapril users only).. Levels of Hb before and after treatment were available for 14,754 patients taking ACE-Is, 751 taking ARBs, and 3087 taking CCBs. A high PDC was significantly associated with greater yearly reductions in Hb levels compared with a low PDC for CCB use, but was more pronounced for ACE-I and ARB use. A high PDC was also associated with a higher odds of developing anemia in ACE-I users (odds ratio [OR], 1.59; P<.001) and ARB users (OR, 2.21; P=.05). In nonanemic enalapril users, every 10-mg increment in daily dose was associated with an OR of 1.45 for the development of anemia (P<.001). The association remained after excluding nonadherent patients.. Levels of Hb are reduced during the first year of use of ACE-Is and to a lesser extent with use of ARBs. This association is dose dependent and is not explained by patient adherence.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Enalapril; Female; Hemoglobins; Humans; Hypertension; Logistic Models; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Retrospective Studies

Topics: Coronary Vessel Anomalies; Enalapril; Humans; Male; Middle Aged; Myocardial Ischemia; Tomography, X-Ray Computed; Treatment Outcome

In patients with coronary artery disease (CAD), therapies designed to prevent clinical events are not always associated with significant reduction in coronary obstruction, as measured by quantitative coronary angiography. We set out to explore the relationship between quantitative coronary angiography parameters, baseline characteristics, and clinical events in a large trial of CAD regression with antihypertensive agents.. Patients randomized to amlodipine, enalapril, or placebo in the CAMELOT trial were followed for 24 months for major ischemic events. Among 431 patients participating in the angiographic and intravascular ultrasound substudy NORMALISE, 298 (99 amlodipine, 96 enalapril, and 103 placebo) had complete angiographic and intravascular ultrasound data. The patients did not differ significantly with respect to baseline characteristics (except for diabetes) or extent of CAD. After 24 months, the change in minimal lumen diameter (MLD) was -0.02 +/- 0.13 for amlodipine, -0.03 +/- 0.12 for enalapril, and -0.03 +/- 0.17 mm for placebo (P = .40). Major ischemic events occurred in 20.2%, 24%, and 25.2%, respectively (P = .68). There was no significant correlation between change in MLD and age, sex, statin therapy, or systolic blood pressure at baseline. The change in MLD did not differ in patients with and without cardiovascular events, regardless of treatment assignment (P = .54). Only the extent of CAD was independently predictive of ischemic events.. As compared to placebo, amlodipine treatment resulted in fewer ischemic events after 24 months of therapy, but the clinical benefit was not associated with a commensurate improvement in arterial lumen dimensions.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Angiography; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Randomized Controlled Trials as Topic; Thrombosis; Treatment Failure; Ultrasonography, Interventional

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Indoles; Myocardial Ischemia; Perindopril; Quinapril; Ramipril; Tetrahydroisoquinolines

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiomyopathy, Dilated; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Muscle, Smooth, Vascular; Myocardial Ischemia; Oxygen Consumption; Pulmonary Wedge Pressure; Severity of Illness Index; Stroke Volume; Treatment Outcome; Vasodilation

Topics: Adaptation, Physiological; Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Enalapril; Myocardial Ischemia; Rats; Severity of Illness Index; Tachycardia

To check wether the deleterious effect of enalaprilat administered before unilateral caroid ligation in the gerbil reported by Fernandez et al. (J Cardiovasc Pharmacol 1994; 24: 937) is not a molecule specific effect but an angiotensin converting enzyme inhibitor class effect.. Survival rate of gerbils (an animal with incomplete Willis hexagona) was measured after unilateral carotid ligation with preadministration (2 hours before by gavage) of saline (0.75 ml) (n = 37); losartan (20 mg/kg) (n = 37), enalaparil (10 mg/kg) (n = 37); a combination of losartan and enalapril at the same dose (n = 37); and of captopril (75 mg/kg) (n = 35).. The survival rate of the gerbils 72 hours after carotid ligation was 65% in control, 62% in losartan, 30% in enalapril, 32% in enalapril + losartan, and 32% in captopril groups. Statistical analysis (log rank test) of the Kaplan-Meier survival curves over 72 hours showed no difference between losartan and controls nor between the various groups treated with ACEI. However survival was significantly lower in the ACEI groups than in the group treated by losartan alone (p < 0.02) or controls (p < 0.02). Intraaortic mean arterial pressure was measured in 6 controls, 6 animals treated with losartan and 6 other treated with enalapril. It was comparable in the losartan and enalapril treated animals (65 +/- 2 mm Hg vs 64 +/- 2) but significantly lower than in the controls (77 +/- 2 mmHg) (p < 0.02).. In contrast to oral preadministration of enalapril and captopril that of losartan does not increase the mortality of the gerbil after unilateral carotid ligation in spite of the same decrease in systemic blood pressure. Although a lower mortality than in controls was not observed with losartan as in the princeps study of Fernandez, these data are consistent with the demonstration by this author that angiotensin II plays a critical protective role in acute ischemia probably by promoting collateral circulation recruitment through non-AT1 receptors stimulation.

Topics: Administration, Oral; Animals; Antihypertensive Agents; Blood Pressure; Captopril; Cardiovascular Surgical Procedures; Carotid Arteries; Disease Models, Animal; Enalapril; Gerbillinae; Ligation; Losartan; Myocardial Ischemia; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Survival Analysis

We investigated whether augmentation of bradykinin (BK) bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated with reduced exercise-induced myocardial ischemia in hypertension.. Bradykinin responses are depressed in hypertension, and endothelial dysfunction contributes to myocardial ischemia by promoting abnormal coronary vasomotion during stress.. Fourteen hypertensive (HT) and 17 normotensive (NT), mildly symptomatic patients with coronary artery disease (CAD) and ST-segment depression during exercise were studied before and after seven days of oral enalapril (EN), which was titrated from 2.5 to 20 mg daily. Patients underwent two treadmill exercise tests and determination of forearm vasodilator response to BK.. Despite receiving a lower dose of EN (7.8 vs. 14.8 mg, p < 0.001), NT patients had a significant reduction in blood pressure compared to HT patients. Compared to pre-EN, the ischemic threshold, defined as the rate-pressure product at the onset of 1-mm ST depression (p = 0.045), the duration of exercise to 1-mm ST depression (180 +/- 54 s, p = 0.007) and the maximum exercise duration (94 +/- 18 s, p < 0.001) were greater after EN in HT patients, but not in NT subjects (all p > or = 0.3). Patients with a greater drop in blood pressure experienced no improvement in exercise-induced ischemia. Forearm blood flow responses to BK were improved with EN in all patients to a similar extent. Moreover, no correlation was observed between the basal response to BK or the magnitude of its improvement with EN and with either the dose of EN or the improvement in exercise ischemic threshold.. Exercise-induced myocardial ischemia is ameliorated in HT patients with CAD by ACE inhibition.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biological Availability; Bradykinin; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Vascular Resistance; Vasodilation

43 patients with mild and moderate arterial hypertension received monotherapy with either stamlo (Dr. Reddy's laboratories, India) in a daily dose 9.5 +/- 0.5 mg (n = 33), or enam (n = 26) in a daily dose 28 +/- 1.5 mg, or stamlo treatment was followed in 10 days by enam (n = 16). Before and after the treatment 24-h monitoring was made of arterial pressure, left ventricular diastolic function and silent myocardial ischemia. Adequate lowering of arterial pressure was observed in 90 and 77% of patients after stamlo and enam treatment, respectively. Stamlo showed more potent antiischemic action and had a positive effect on left ventricular filling.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Coronary Circulation; Diastole; Drug Therapy, Combination; Electrocardiography; Enalapril; Humans; Hypertension; Middle Aged; Myocardial Ischemia; Ventricular Function, Left

To test the ability of ACE inhibitor berlipril to control neurohumoral hyperactivation and reestablish balance between oxidant and antioxidant systems in patients with ischemic heart disease (IHD) associated with heart failure (HF).. 145 patients (mean age 51.5 +/- 3.94 years) with IHD class II-III associated with circulatory insufficiency NYHA class II-III received berlipril for 6 weeks.. Berlipril treated patients exhibited decreased class of HF, improved left ventricular conductivity, attenuated neurohumoral stimulation, intensity of cell membrane peroxidation, increased plasmic pool of antioxidant enzyme systems.. 6-week berlipril treatment promoted a pronounced improvement of neurohormonal profile of plasm and recovery of free radical lipid peroxidation which resulted in reduction of HF.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Catecholamines; Echocardiography; Enalapril; Free Radical Scavengers; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Lipid Peroxidation; Middle Aged; Myocardial Ischemia; Treatment Outcome

The effect of angiotensin-converting enzyme (ACE) inhibitors on ischemia-induced spatial dispersion of ventricular repolarization was investigated in 12 pentobarbitone-anesthetized sheep. The obtuse marginal coronary artery was occluded in the pretreated animals (enalapril maleate, 0.4 mg/kg, i.v., n = 6) and controls (normal saline, i.v., n = 6). The activation-recovery intervals were determined from the unipolar ECGs acquired from the ischemic region. There was a significant increase in the pooled activation-recovery interval dispersion in both groups at 30 min of coronary occlusion (p < 0.01), however, the increase in the treatment group was smaller than that of the controls (15.9 +/- 9.7 vs. 43.6 +/- 19.9 ms, p < 0. 01). Ventricular ectopic beats were observed in the 6 controls and in only 1 pretreated animal.. ACE inhibitors suppress the spatial dispersion of ventricular repolarization and this may be attributed to, at least in part, its antiarrhythmic effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Coronary Disease; Electrocardiography; Enalapril; Female; Male; Myocardial Ischemia; Sheep; Ventricular Function; Ventricular Premature Complexes

It is not yet known if the alterations in myocardial glucose metabolism and the exaggerated left ventricular dysfunction that occur during reperfusion in hypertrophied hearts are reversible. Thus, we studied isolated working hearts from aortic-banded (n = 29) and sham-operated control (n = 32) male Sprague-Dawley rats with or without enalapril maleate treatment (25.6 +/- 0.8 mg/kg per day, p.o.) to determine the effect of regression of cardiac hypertrophy on myocardial glucose metabolism and post-ischemic heart function. Hearts were perfused with buffer containing 1.2 mM palmitate, 11 mM [5-3H]/[U-14C]-glucose, 0.5 mM lactate and 100 microU/ml insulin. Glucose metabolism [rates of glycolysis (3H2O production) and rates of oxidation (14CO2 production) of exogenous glucose] and heart function (heart rate x peak systolic pressure) were measured during 30 min pre-ischemic perfusion and 60 min of reperfusion following 20 min of global, no-flow ischemia. Hearts from untreated aortic-banded rats were hypertrophied, being 27.6 +/- 1.8% larger than hearts from untreated control rats. Enalapril treatment caused regression of cardiac hypertrophy that normalized heart weight in aortic-banded rats. Rates of glycolysis of exogenous glucose in hearts from untreated aortic-banded rats were accelerated compared to rates in hearts from untreated control rats during pre-ischemic perfusion (4391 +/- 97 v 2652 +/- 69 nmol glucose/min per g dry wt, respectively, P < 0.05) and reperfusion (2402 +/- 58 v 1597 +/- 88 nmol glucose/min per g dry wt. respectively, P < 0.05). In contrast, rates of glycolysis of exogenous glucose in hearts from enalapril-treated aortic-banded rats were normalized before and after ischemia. Rates of glycolysis of exogenous glucose in hearts of control rats were not affected by enalapril treatment. Oxidation of exogenous glucose was not different among groups either before or after ischemia. Function of hearts from untreated aortic-banded rats at the end of reperfusion was significantly less than that of hearts from untreated control rats (23.9 +/- 2.6 v 32.2 +/- 0.7 mmHg x beats per min/1000, respectively, P < 0.05). As with myocardial glucose metabolism function of hearts from aortic-banded rats treated with enalapril was normalized during reperfusion. Thus, pharmacologically induced regression of pressure-overload cardiac hypertrophy normalizes glucose metabolism as well as left ventricular function during reperfusion.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Enalapril; Glucose; Glycolysis; Hypertrophy, Left Ventricular; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Organ Size; Oxidation-Reduction; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

The hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)bipheneoyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a new angiotensin II type 1 receptor antagonist, on rats with myocardial infarction induced by coronary artery ligation was examined. Four weeks after ligation, mean blood pressure, left ventricular pressure and cardiac output decreased, while left ventricular end-diastolic pressure increased in control rats. Left ventricular end-diastolic pressure significantly decreased in rats treated with valsartan at 30 mg/kg/d p.o. for 4 weeks. Total systemic resistance remarkably decreased in those with enalapril 3 mg/kg/d p.o. and valsartan 30 mg/kg/d p.o. Valsartan and enalaprilat did not affect cardiac functions of isolated intact rat hearts before and after ischemia in Langendorff apparatus. In addition to hemodynamic effects observed in vivo, valsartan at 30 mg/kg p.o. significantly inhibited left ventricular hypertrophy. Valsartan would thus appear to be clinically useful for treating heart failure following myocardial infarction.

Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiomegaly; Enalapril; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Organ Size; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Valine; Valsartan; Vascular Resistance; Ventricular Function, Left

Topics: Aged; Angina Pectoris; Blood Pressure; Case-Control Studies; Coronary Circulation; Enalapril; Exercise Test; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Oxygen Consumption

We wished to elucidate the effects of the calcium-sensitizing positive inotropic agent MCI-154 and its combined use with an angiotensin-converting enzyme (ACE) inhibitor enalapril on postischemic contractile dysfunction. Anesthetized dogs underwent a 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Regional myocardial segment shortening in the ischemic LAD area was assessed by sonomicrometry. Myocardial segment shortening decreased in response to the LAD occlusion and remained decreased during 2-h reperfusion. The intravenous infusion of MCI-154 (0.1 or 0.3 micrograms/kg/min) initiated 10 min after occlusion and throughout reperfusion significantly improved the recovery of segment shortening. The alleviation of the postischemic contractile dysfunction by MCI-154 was augmented when the animals were treated with a bous injection of enalapril (0.3 mg/kg) 15 min before ischemia followed by an infusion of the drug (0.003 mg/kg/min). The pretreatment with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01 mg/kg/min) did not alleviate the postichemic dysfunction, however, although it decreased systemic blood pressure (BP). Ischemic bed size, myocardial necrosis (by triphenyltetrazolium chloride staining), and collateral blood flow (by colored microspheres) were similar in all experimental groups. These results indicate that MCI-154 improves the postischemic contractile function of dog heart, whereas enalapril fails to improve it. ACE inhibitors may also augment the efficacy of cardiotonics on postischemic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Calcium; Cardiotonic Agents; Coronary Circulation; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Enalapril; Female; Infusions, Intravenous; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Pyridazines

In rats, chronic administration of the nitric oxide (NO) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) causes arterial hypertension, cardiac hypertrophy and myocardial ischemic alterations such as necrosis and fibrosis. In this study, we evaluated the effect of 8 weeks of treatment with enalapril maleate on cardiac weight and on the development of the histological alterations induced by L-NAME. Enalapril significantly inhibited the development of both arterial hypertension (117.2 +/- 5.8, 161.8 +/- 8.8 and 122.0 +/- 10.6 mm Hg, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively) and left ventricular hypertrophy (1.36 +/- 0.13, 1.60 +/- 0.04 and 1.48 +/- 0.05 mg/g, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively), but had no effect on the myocardial lesions. These findings demonstrate that although the renin-angiotensin system plays a major role in the development of arterial hypertension and cardiac hypertrophy, it does not modulate the ischemia-induced myocardial alterations observed in this model.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arginine; Enalapril; Heart; Male; Myocardial Ischemia; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Size; Rats; Rats, Wistar

We evaluated, firstly, the sensitivity to cardiac ischemic ATP breakdown during the development of hypertension and cardiac hypertrophy in Spontaneously Hypertensive Rats (SHR) v Wistar Kyoto (WKY) controls, and secondly, the effects of short-term (8 days) and prolonged (3 months) antihypertensive treatment with the angiotensin converting enzyme inhibitor enalapril on hypertrophy and sensitivity to global ischemia. In isolated perfused hearts, ischemia was induced by a stepwise lowering of the perfusion pressure and the appearance of the ATP breakdown products (purines) in the coronary effluent was assessed as a measure of ischemia. Hearts from 2.5- and 4-month-old SHR started to release purines at a higher perfusion pressure than hearts of WKY, associated with a higher maximum concentration in the coronary effluent. This increased ischemic ATP breakdown in 2.5- and 4-month-old SHR could be attributed to a decreased flow at a given perfusion pressure, because of a two-fold increase in coronary vascular resistance (CVR). In contrast, the maximal purine concentration in the coronary effluent in hearts of 7-month-old SHR was reduced compared to the younger SHR and only slightly higher than 7-month-old WKY, despite a persistent increase in CVR. Enalapril normalized the blood pressure, but only prolonged treatment, significantly prevented and regressed cardiac hypertrophy, and reduced CVR. Whereas enalapril did not influence ATP breakdown in WKY, in SHR both short- and long-term treatment normalized it to the pattern observed in WKY. We conclude that during the early phase of cardiac hypertrophy the hearts of SHR become more sensitive to ischemic ATP breakdown solely because of an increase in CVR, whereas during the established hypertrophic phase, the hearts appear to adapt metabolically, resulting in normalized purine release. Enalapril normalized the transient increase in sensitivity to ischemic ATP breakdown during the development of hypertension in SHR, independent of effects on cardiac hypertrophy, apparently by improving coronary flow at low perfusion pressures.

Topics: Adenosine Triphosphate; Aging; Animals; Blood Pressure; Enalapril; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardial Ischemia; Purines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Vascular Resistance

Ten patients with severe (NYHAIII) heart failure were compared with 10 age-matched healthy subjects in terms of oxygen uptake and minute ventilation at rest and during exercise and calf and forearm blood flow measured by venous occlusion plethysmography at rest and after a standardized exercise test. Patients performed a symptom-limited treadmill exercise test and were then treated with enalapril for 5 weeks; the various measurements were repeated at weekly intervals. Oxygen consumption (VO2) at rest was similar in the patients and controls. During exercise, patients VO2 tended to be lower at each workload, but this was not affected by enalapril treatment. Minute ventilation was higher at rest and at each exercise stage in the patients than in the control subjects, and this was significantly reduced by enalapril treatment. Compared with the controls (2.94 +/- 0.10 and 2.93 +/- 0.20 ml.100 ml-1.min-1) forearm and calf blood flow measured by venous occlusion plethysmography was reduced at rest in the patients (1.34 +/- 0.18 and 1.24 +/- 0.11 ml.100 ml-1.min-1). but was significantly increased by enalapril treatment (1.73 +/- 0.15 and 1.60 +/- 0.16 ml.100 ml-1.min-1). Submaximal leg exercise to a fixed VO2 showed attenuation of the normal vasoconstriction in the forearm and vasodilatation of the calf; enalapril treatment changed these responses significantly towards normal but a marked abnormality of flow pattern persisted.

Topics: Aged; Arm; Cardiomyopathy, Dilated; Enalapril; Exercise Test; Exercise Tolerance; Humans; Leg; Male; Middle Aged; Muscles; Myocardial Ischemia; Oxygen Consumption; Regional Blood Flow; Respiration