enalapril and Hypertrophy--Left-Ventricular

This article focuses on the potential role of mineralocorticoid receptor antagonists (MRAs) in patients with stage B heart failure (HF) due to hypertension, diabetes mellitus, and/or visceral obesity with the metabolic syndrome. It briefly discusses the role of MRAs in patients with left ventricular dilatation due to nonischemic or ischemic cardiomyopathy and in those with a prior myocardial infarction but without left ventricular dilatation or evidence of HF.

Topics: Adrenal Glands; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Endothelium, Vascular; Glomerular Filtration Rate; Heart Failure; Humans; Hydrocortisone; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Potassium; Spironolactone

Left ventricular hypertrophy (LVH) is a strong, independent predictor of cardiovascular events and all-cause mortality. Patients with LVH are at increased risk for stroke, coronary heart disease, congestive heart failure, and sudden cardiac death. Hypertension is a major influence on the development of LVH. The prognostic power of LVH is likely multifactorial. LVH represents both a manifestation of the effects of hypertension and other cardiac risk factors over time as well as an intrinsic condition causing pathologic changes in cardiac structure and function. Angiotensin II plays a central role in the development of LVH. Several antihypertensive treatments, especially angiotensin II receptor blockers, can reverse LVH and improve cardiovascular outcomes independent of blood pressure reduction. Further studies are required to determine if these agents should become first-line therapy for all patients with hypertension and LVH.

Topics: Adrenergic Antagonists; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Carbazoles; Carvedilol; Chi-Square Distribution; Cohort Studies; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Drug Therapy, Combination; Echocardiography; Electroencephalography; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Logistic Models; Losartan; Male; Multivariate Analysis; Prognosis; Propanolamines; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Risk Factors; Sex Factors; Stroke; Survival Analysis; Telmisartan

In arterial hypertension, left ventricular (LV) hypertrophy (H) is a prognostically relevant target organ damage associated with systolic and diastolic LV dysfunction. The level of LV dysfunction seems to be related to the degree of myocardial fibrosis. Prognosis of hypertensive patients who have LVH regression appears to be improved. Therefore, LVH regression is an important antihypertensive treatment goal. The renin-angiotensin-aldosterone system is implicated in LVH development and myocardial fibrosis in essential arterial hypertension. Early studies in the 80s and 90s have led expectations that angiotensin converting enzyme (ACE) inhibitors could induce greater LVH regression than other antihypertensive drugs at similar blood pressure reduction. In the late 90s, the double-blind randomized controlled PRESERVE trial (Prospective Randomize Enalapril Study Evaluating Reversal of Ventricular Enlargement) has been designed to evaluate whether the ACE inhibitor enalapril was more effective than nifedipine GITS in regressing LVH and improving LV diastolic dysfunction. The PRESERVE study demonstrated a mildly higher antihypertensive effect of nifedipine GITS than enalapril, which required more frequently association with hydrochlorothiazide to control blood pressure. However, at similar level of blood pressure reduction achieved with enalapril and long-acting nifedipine in association with hydrochlorothiazide or atenolol, both antihypertensive treatments showed similar efficacy in LVH regression and LV diastolic filling improvement.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Dihydropyridines; Disease Models, Animal; Diuretics; Drug Therapy, Combination; Enalapril; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Meta-Analysis as Topic; Nifedipine; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Sodium Chloride Symporter Inhibitors; Time Factors; Ventricular Dysfunction, Left

Left ventricular hypertrophy (LVH) is a clinical condition associated with an increased risk of vascular events. Several trials have been done to evaluate the action of different antihypertensive treatments on the regression of LVH IN HYPERTENSIVE PATIENTS. The efficacy of diuretics in the reduction of LVH is controversial. The LIVE study (Left Ventricular Hypertrophy Regression: Indapamide Versus Enalapril) is a European, prospective, double-blind, randomised, controlled trial aimed to compare the efficacy of indapamide 1.5 mg daily with that of enalapril 20 mg daily in the reduction of LVH in hypertensive patients (systolic blood pressure > 160 and < 210 mmHg) with LVH (left ventricular mass index 120 g/m2 in men and > 100 g/m2 in women) after 1 year of treatment. The assessment of LVH was done by echocardiography. A blind randomised reading of the echo recordings was performed at the end of the study by an independent Core Echocardiography Committee with three readers. Preliminary data are available from this trial. These data confirm the antihypertensive efficacy of indapamide and its efficacy in the reduction of left ventricular mass through a progressive action over 1 year.

Topics: Antihypertensive Agents; Clinical Trials as Topic; Enalapril; Humans; Hypertrophy, Left Ventricular; Indapamide; Remission Induction

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

Benefit achieved through use of angiotensin converting enzyme (ACE) inhibitors in patients with reduced left ventricular (LV) systolic function is not confined to those with clinical manifestations of heart failure. Although rates of adverse clinical events are lower in asymptomatic patients, within this population ACE inhibitors have been shown to prevent adverse ventricular remodelling, prevent the development of clinical heart failure, reduce rates of hospitalization for heart failure and, in some studies, reduce mortality. Most of the benefit derived appears to be associated with preventing the progression of LV hypertrophy, dilatation, and dysfunction, resulting in prevention of heart failure. Additionally, the incidence of myocardial infarction is decreased, although the exact physiological basis for this benefit remains uncertain. Given the enormity and growth of heart failure as a public health problem and the potential for influencing the underlying pathophysiology, ACE inhibitor treatment offers substantial benefit for patients with asymptomatic LV systolic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiac Volume; Drug Administration Schedule; Enalapril; Heart Failure; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

Left ventricular hypertrophy (LVH) is a recognized complication of, rather than a physiological response to, hypertension, being a powerful independent indicator of cardiovascular disease risk. In addition, it is reasonable to assume that the reversal of LVH is a desirable therapeutic goal in the treatment of hypertension. Furthermore, the renin-angiotensin system plays an important role in LVH and, in particular, in the development of cardiac interstitial fibrosis. Therefore, the effect of angiotensin-converting enzyme (ACE) inhibition on LVH is of particular interest. In both experimental and human studies, ACE inhibitors appear to perform better than other antihypertensive agents in reversing cardiac structural changes. A recent meta-analysis showed ACE inhibitors to be more efficacious than other first-line antihypertensives in reducing left ventricular mass. A controlled long-term study of previously untreated men showed that enalapril reversed LVH significantly better than did hydrochlorothiazide and that the regression of LVH was independently related to blockade of the renin-angiotensin system. Indeed, there have been studies showing that ACE inhibitors can affect LVH without lowering blood pressure. Moreover, ACE inhibitors have shown cardioprotective and cardioreparative properties in experimental models of hypertensive LVH. In conclusion, ACE inhibitors are effective in reversing LVH as well as interstitial fibrosis. The prognostic implications of this remain to be seen. So far, the experience with spirapril on LVH is limited, but the accumulated data are promising.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular

Hypertension-induced cardiac dysfunction is variable among different anti-hypertensive medications. This study compares the effects of telmisartan and enalapril on echocardiographic parameters in hypertensive patients.. This was a randomised single blinded study. Eighty hypertensive patients were included in this study and they were randomly allocated into two study groups: Group 1 included 40 patients who took telmisartan 80mg once daily for six months. Group 2 included 40 patients who took enalapril, 20mg once daily for six months. An additional 40 healthy participants were enrolled in the study as controls (Group 3). Baseline echocardiographic scan was done at the start of the study and after 6 months of treatment including assessment of left ventricular systolic and diastolic functions with assessment of left ventricular mass index, in addition to measurements of blood pressure, heart rate and double product.. Both group 1 and group 2 (telmisartan and enalapril groups respectively) showed comparable statistically significant improvement in the diastolic functional parameters (P<0.010), while both medications didn't demonstrate changes in the systolic functional parameters. Furthermore, telmisartan was significantly effective in reducing the interventricular septal thickness and left ventricular mass index (P<0.010).. Both drugs interfere with renin-angiotensin aldosterone system, protecting the myocardium from high blood pressure. Findings from our study provide key results for physicians in deciding the appropriate antihypertensive drug for each patient depending based on the patient's intolerability for either medication.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Echocardiography, Doppler; Enalapril; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Retrospective Studies; Single-Blind Method; Telmisartan; Treatment Outcome; Ventricular Function, Left

Cardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been demonstrated. The present protocol describes a trial to test the efficacy of bedtime dosing of the ACE inhibitor enalapril on night time blood pressure and left ventricular mass in patients with type 1 diabetes.. In a randomised, double-blind, two-way cross-over study, 24 normoalbuminuric patients with type 1 diabetes with CAN will be treated for 12 weeks with either morning or bedtime dosing of 20 mg enalapril, followed by 12 weeks of switched treatment regimen. During each treatment period, two 24 h ambulatory blood pressure measurements will be performed and after each treatment period left ventricular mass will be determined by multisliced CT. Primary end points will be reduction in blood pressure and reduction in left ventricular mass.. The study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (the Good Clinical Practice Unit at Copenhagen University Hospital) will oversee the study. The results of the study will be presented at national and international scientific meetings and publications will be submitted to peer-reviewed journals.. EudraCT (2012- 002136-90).

Topics: Adult; Aged; Antihypertensive Agents; Autonomic Nervous System Diseases; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Double-Blind Method; Drug Chronotherapy; Enalapril; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Multidetector Computed Tomography; Organ Size; Young Adult

High levels of activity of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) are related to left ventricular hypertrophy (LVH). A percentage of subjects with hyperactivity to treadmill stress test show LVH to echocardiogram. This paper aims at evaluating neurohumoral influence over these subjects by comparing drugs that block both the RAS and the SNS. In a 1-year open protocol, 195 normotensive subjects, with hyperactivity to treadmill stress test and LVH, were randomly assigned to supervised physical exercise, rilmenidine 1 mg day(-1), atenolol 50 mg day(-1), enalapril 10 mg day(-1) or losartan 50 mg day(-1). Changes in left ventricular mass index (LVMI), measured by means of echocardiogram, were the primary end point. Changes in systolic blood pressure (SBP) at rest and peak effort were also evaluated. Enalapril significantly brought LVMI down in relation to the basal value (28.2%; n=36) similarly to losartan (26.9%; n=42); P>0.05. However, both were more efficient than physical exercise (2.9%; n=39), rilmenidine (5.1%; n=38) and atenolol (7.2%; n=40); P<0.001. There was no significant difference in SBP reduction at rest and peak effort in groups assigned to atenolol, enalapril and losartan; P>0.05. In such groups, reduction was greater than in groups assigned to physical exercise and rimenidine; P<0.001. In conclusion, drugs that block RAS were more efficient in reducing LVH than physical exercise and drugs that block SNS, and such reduction took place regardless of SBP level reduction at rest and peak effort.

Topics: Adult; Antihypertensive Agents; Atenolol; Blood Pressure; Enalapril; Exercise Test; Exercise Therapy; Female; Humans; Hypertrophy, Left Ventricular; Losartan; Male; Oxazoles; Renin-Angiotensin System; Rilmenidine; Sympathetic Nervous System

To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis.. Hypertensive patients (n = 196) with echocardigraphically documented left ventricular hypertrophy were randomized to candesartan 8-16 mg/day (n = 91) or enalapril 10-20 mg/day (n = 105) with possible addition of hydrochlorothiazide (12.5-25 mg/day) for 48 weeks. Echoreflectivity analysis was performed on ultrasound two-dimensional tracings of the midapex septum with a specifically designed and validated software. Colour histograms were obtained; the primary outcome variable was the treatment-related change in histogram width (broadband), previously shown to correlate with collagen volume on endomyocardial biopsy; changes in mean colour scale were secondary outcome variable.. Echoreflectivity analysis was feasible in 84 patients (48 candesartan, 36 enalapril). Broadband decreased significantly in the candesartan (-8.0 colour levels) and in the enalapril group (-12.9 colour levels) with no significant difference between treatments (P = 0.409); no significant changes occurred in mean colour scale. Patients under monotherapy (n = 46) showed similar trends as the larger intention to treat cohort, without significant difference between treatments.. In hypertensive patients with left ventricular hypertrophy, both candesartan and enalapril induce a moderate but statistically significant reduction in an echoreflectivity index of myocardial fibrosis.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Enalapril; Female; Fibrosis; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardium; Tetrazoles; Treatment Outcome; Ultrasonography

To evaluate the effect of ACE inhibitor enalapril, AR blocker candesartan and their combination on left ventricular hypertrophy (LVH) and content of biochemical markers of collagen balance in patients with hypertensive LV hypertrophy. MATERIAL AND METHODS. A total of 66 patients with arterial hypertension with LV hypertrophy were divided into two groups. Group 1 (n = 33) received candesartan (8-16 mg/day), group 2 (n = 33) received enalapril (10-20 mg/day). In effective hypotensive response to the initial treatment, it was continued for 6 months. If in two months of monotherapy the effect was unsatisfactory, the other drug was added. At baseline and upon 6 months of treatment all the patients were examined for myocardial mass index (MMI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (THMP-1) in the blood.. In effective initial treatment with candesartan 6-month treatment lowered LV MMI by 13.9%, while in enalapril group--only by 1.5%. In addition of the second drug in ineffective initial therapy the reduction was 5.1%. THMP-1 did not change during the trial.. In patients with hypertensive LVH candesartan more effectively treated LVH. The addition of the second RAS blocker in insufficient efficacy of the initial one significantly reduces LV MMI. A significant antifibrotic effect was achieved only in case of simultaneous use of two RAS blockers.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Biomarkers; Biphenyl Compounds; Blood Pressure; Collagen; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 1; Middle Aged; Renin-Angiotensin System; Tetrazoles; Tissue Inhibitor of Metalloproteinase-1; Treatment Outcome

In order to evaluate the effect of enalapril on haemodynamics and renal function in a pressure overload model, we prepared eight feline models of left ventricular hypertrophy (LVH) by banding of the aortic arch. The LVH cats were assigned to the placebo group or the enalapril group (0.5 mg/kg, PO, sid) 3 months following surgery, and each received its respective drug for 4 weeks. Each week, blood pressure, angiotensin converting enzyme (ACE) activity in blood, and creatinine clearance were measured, and complete blood count (CBC), biochemical examination of the blood, echocardiography, and chest radiography were carried out. The interventricular septum thickness (IVSd, IVSs), fractional shortening (FS), and ejection fraction (EF) increased significantly in the LVH cats following surgery (P<0.05). There was no significant difference between the placebo group and the enalapril group with respect to general physical parameters, CBC, biochemical parameters and renal function. In the enalapril group, systolic arterial pressure, mean arterial pressure, and ACE activity in blood decreased significantly following administration (P<0.05). In addition, the left ventricular free wall thickness in diastole and IVSd decreased significantly following administration (P<0.05). These results suggest that, in a pressure overload model, enalapril (0.5 mg/kg, sid) inhibits cardiac hypertrophy, reduces blood pressure, and does not adversely affect renal function.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cat Diseases; Cats; Enalapril; Hypertrophy, Left Ventricular; Models, Animal; Ventricular Function, Left

Ambulatory blood pressure (BP) is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH).. In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52.. At study end, both treatments significantly improved ambulatory BP compared with baseline (p < or = 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) significantly more than enalapril treatment (p < 0.01). No significant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was significantly reduced (-9.1 g/m2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted.. First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Male; Middle Aged; Perindopril; Prospective Studies; Time Factors; Treatment Outcome

Angiotensin-converting enzyme (ACE) inhibition attenuates ventricular remodeling and improves ventricular function in heart failure patients. Vasopeptidase inhibition has shown similar effects in experimental models.. The OVERTURE echocardiographic study was designed to test the hypothesis that the vasopeptidase inhibitor omapatrilat would attenuate ventricular remodeling and improve ventricular function to a greater extent than an ACE inhibitor.. Three hundred twenty-one patients with heart failure (New York Heart Association class > or = 2) were included in the OVERTURE echocardiographic substudy and were randomized to receive enalapril (10 mg twice a day) or omapatrilat (40 mg every day). Echocardiograms were performed at baseline and at 1 year (n = 214). Left ventricular size was estimated by summation of ventricular areas in apical and short-axis views and by calculation of ventricular volumes. Ejection fraction was calculated from ventricular volumes.. Combined diastolic and systolic areas and volumes decreased significantly (mean diastolic area change -8.36 cm2, 95% CI -9.4 to -7.3 cm2; mean systolic change -8.4 cm2, 95% CI -9.5 to -7.3 cm2), and ejection fractions increased significantly (3.6%, 95% CI 2.6% to 4.6%) in both treatment groups from baseline to 1 year. There were no differences in the magnitude of improvement in ventricular size or function based on treatment assignment. Patients who died or were hospitalized for heart failure subsequent to the final assessment demonstrated the least degree of reverse remodeling.. Ventricular size and function improved similarly after 1 year with ACE or vasopeptidase inhibition in patients with heart failure. Reverse remodeling was associated with improved outcome.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cohort Studies; Enalapril; Female; Heart Failure; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Neprilysin; Organ Size; Proportional Hazards Models; Protease Inhibitors; Pyridines; Reproducibility of Results; Stroke Volume; Survival Analysis; Thiazepines; Treatment Outcome; Ultrasonography; Ventricular Remodeling

Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. In patients with hypertension and LVH, both an angiotensin converting enzyme (ACE) inhibitor and an angiotensin type 1 receptor (AT1) antagonist regress LVH. However, it remains controversial whether dual blockade of the renin-angiotensin system will regress LVH in these patients using a combination of ACE inhibitor and AT1 antagonist. Thirty-three type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy and were diagnosed as having LVH evaluated by echocardiography were selected from three dialysis units staffed by the faculty of Saitama Medical School, Saitama, Japan between 1999 and 2001. The study was carried out for 1 year. All patients were assigned randomly to three groups with equal number: group I, an ACE inhibitor, enalapril 10 mg daily; group II, an AT1 antagonist, losartan 100 mg daily; group III, combination of enalapril 10 mg and losartan 100 mg daily. All antihypertensive drugs were given 30 min after the cessation of dialysis therapy. LVH was evaluated by echocardiography before the start of administration of drugs, at 6 months and 12 months after the start of drug therapy. Systolic blood pressure levels less than 140 mmHg were the target for the three groups. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive decreases over time in left ventricular mass index, posterior wall thickness and interventricular septum thickness. There were no significant differences in regression of LVH as well as blood pressure control between enalapril and losartan groups; however, dual blockade induced an additional 28% reduction in left ventricular mass index compared with any type of monotherapy. Both ACE inhibitors and AT1 antagonists benefit the regression of LVH in diabetic patients who start dialysis therapy. Moreover, combination therapy with ACE inhibitors and AT1 antagonists would provide more beneficial effects on LVH in these patients than monotherapy.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Renin-Angiotensin System; Treatment Outcome

Large trials on left ventricular hypertrophy (LVH) regression are indispensable to allow accurate evaluation of the different classes of treatments. Such a trial, the LIVE study, gave us the opportunity to examine the influence of the mode of reading of the echo tracings on results and to underline the value of two initial recordings performed at entry.. The LIVE study was designed to compare 1.5 mg indapamide SR with 20 mg enalapril on the regression of LVH evaluated echocardiographically. M-mode tracings of the left ventricle were performed at selection and after a 2 week placebo run-in. Recordings were read by investigators and by three experts all through the study, and finally read again by the three experts blind to treatment and sequence.. The two initial examinations produced an estimate of the reproducibility of the measurement of the left ventricular mass (LVM) that can be proposed as an indicator of overall quality provided no patients are excluded. The standard deviation of the differences between these two estimates of LVM was 52 g. These two examinations may also help quantify regression to the mean, which was not significant for the whole group. Knowledge of the sequence of examinations overestimates the change in LVM with treatment, as shown by comparison of measurements carried out during quality control with the measurements made blind (-19 +/- 52 versus -6 +/- 53 g, P <0.01).. The comparison of two initial echoes at entry allow one to define a quality criteria for such trials and to quantify a possible regression to the mean. The reading of recordings with knowledge of sequence significantly overestimates LVM variations on treatment.

Topics: Antihypertensive Agents; Delayed-Action Preparations; Double-Blind Method; Echocardiography; Enalapril; Female; Humans; Hypertrophy, Left Ventricular; Indapamide; Male; Remission Induction

This study sought to validate the reliability of serial echocardiographic measurements in detecting left ventricular (LV) hypertrophy regression by using magnetic resonance imaging (MRI) as a reference standard.. We studied a small population (n = 20) of patients enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial for evaluating LV hypertrophy regression. LV mass was measured by both echocardiography and MRI at baseline and after 1 year. As compared with baseline, systolic and diastolic blood pressures were significantly decreased after 1 year (all P <.05). Echocardiographic technique showed an overestimation of LV mass by 27.6 g at baseline (P =.005) and by 37.1 g after 1 year (P <.001), and there were wide 95% limits of agreement (+/-36.0 g at baseline; and +/-27.6 g after 1 year) when compared with MRI measurement. Significant changes of LV mass from baseline of -20 +/- 22 g (P<.01) and -29 +/- 19 g (P <.01) were detected by using echocardiography and MRI after 1 year, respectively (P =.02), and there were similarly wide limits of agreement for change in LV mass (+/-24.2 g).. Despite the use of careful methodology, echocardiographic measurement of LV mass at a single time point or for serial studies resulted in significant variation in LV mass estimates from measurement using MRI.

Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Nifedipine

Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events.. We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis.. In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P =.002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events.. In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all, of the effect of enalapril in this study.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Electrocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nisoldipine; Proportional Hazards Models; Prospective Studies

Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension.. A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone.. Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Enalapril; Eplerenone; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardium; Potassium; Renin-Angiotensin System; Spironolactone; Treatment Outcome

CARDIOVASCULAR RISK OF LEFT VENTRICULAR HYPERTROPHY: Because of the rhythmic, mechanical and ischemic risk related to it, the left ventricular hypertrophy (LVH) is considered to be a major independent risk factor for cardiovascular disease which should be screened for and treated early. In patients with type 2 diabetes, left ventricular hypertrophy is mainly due to high blood pressure, but also to reduced elasticity of the large vessels, defective vasomotricity and dysfunction of the arterial endothelium. Obesity, elevated blood viscosity, hyperinsulinism and/or autonomous cardiac neuropathy can also have a favoring effect. THE LIVE STUDY: Is the first multicentric European study comparing the efficacy of a thiazide-like diuretic, slow-release indapamid, with a converting enzyme inhibitor, enalapril 20 mg, on the reduction of the left ventricular mass index (LVMI) in hypertensive subjects with LVH. The study involved a randomized centralized reading of the echocardiograms as well as a randomized and blinded reading at the end of the study. DEMONSTRATED SUPERIORITY OF INDAPAMID SR: The LIVE study clearly demonstrated the superiority of indapamid SR over enalapril 20 mg in reducing the LVMI in hypertensive subjects with LVH while the blood pressure lowering effect was comparable for the two treatments.

Topics: Adrenergic alpha-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Doxazosin; Drug Therapy, Combination; Echocardiography; Electrocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Placebos; Prazosin; Prognosis; Prospective Studies; Risk Factors; Time Factors

Fibrosis of left ventricle commonly occurs in end stage renal disease(ESRD) patients and is an independent risk factor of cardiovascular events. Angiotensin II type 1 receptor antagonist may be able to reverse fibrosis of left ventricle in ESRD patients. Ultrasonography-integrated backscatter(IBS) of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. In this study, 30 chronically hemodialyzed patients with hypertension were randomly allocated to receive antihypertensive therapy with either angiotensin II type 1 receptor(AT1-R) antagonist losartan(n = 10), angiotensin-converting enzyme(ACE) inhibitor enalapril(n = 10) or calcium antagonist amlodipine(n = 10). IBS of posterior wall of left ventricule were measured by IBS before and after 6 months treatment. Baseline demographic and clinical characteristics did not differ in three subgroups. Although losartan(34.2 +/- 1.8 to 30.2 +/- 2.4 dB: p = 0.0094) treatment demonstrated significant reduce of IBS values, enalapril(30.3 +/- 1.5 to 31.7 +/- 1.4 dB: p = 0.3268) and amlodipine (31.6 +/- 1.6 to 33.1 +/- 1.9 dB: p = 0.4632) did not changed it significantly before and after 6 months treatment. All three groups reduced left ventricular mass index(Losartan 154.5 +/- 9.9 to 114.6 +/- 5.8 g/m2: p = 0.0002) (enalapril 155.6 +/- 14.3 to 135.3 +/- 10.4 g/m2: p = 0.0275) (amlodipine 156.6 +/- 7.3 to 137.2 +/- 4.1 g/m2: p = 0.0589). Three groups manifested a similar significant decrease in the mean blood pressure. Plasma angiotensin II concentration was markedly increased by 5.0-fold relative to the control levels before treatment in Losartan treatment, in contrast unchanged in enalapril and only 2.0-fold increased in amlodipine treatment. This study indicates that losartan reduce of fibrosis of left ventricule and this effect may be via an anti-AT1-R effect.

Topics: Amlodipine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiomyopathies; Enalapril; Female; Fibrosis; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Losartan; Male; Middle Aged; Myocardium; Renal Dialysis

A limited number of studies have evaluated the effect of angiotensin II receptor antagonists (AIIAs) on left ventricular hypertrophy (LVH) in comparison with other antihypertensive drugs, and no large study has compared AIIAs with angiotensin-converting enzyme inhibitors (ACEIs).. The CATCH (Candesartan Assessment in the Treatment of Cardiac Hypertrophy) study was a multicenter prospective randomized double-blind trial comparing the effects of candesartan cilexetil (8-16 mg once daily) and enalapril (10-20 mg once daily) with possible addition of hydrochlorothiazide (12.5-25 mg once daily) on echocardiographic left ventricular mass index (LVMI), in 239 hypertensives with LVH (LVMI 120 g/m2 in men and 100 g/m2 in women). Two-dimensionally guided M-mode echocardiograms were carried out at screening (recruiting scan), randomization (baseline scan) and after 24 and 48 weeks of treatment. Baseline and treatment echocardiograms were read at two central labs without knowledge of the scan time sequence. In intention-to-treat (ITT) analyses (196 patients), systolic and diastolic blood pressures (SBP, DBP) were significantly and equally reduced by the two treatments. Candesartan and enalapril reduced LVMI to the same extent, i.e. by 15.0 and 13.1 g/m2 (-10.9 and -8.4%; P<0.001 for both). The proportion of patients achieving normalization of LVMI was non-significantly higher with candesartan (36.3 versus 28.6%). Similar results were obtained in per-protocol (PP) analyses. Cough incidence was lower with candesartan ( P<0.03).. CATCH is the first large study comparing the effects of an AIIA and an ACEI on LVMI. Candesartan cilexetil was found to be equally effective as enalapril in reducing SBP, DBP and LVMI in hypertensives with LVH, according to both ITT and PP analyses.

Topics: Adult; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Echocardiography; Enalapril; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Tetrazoles; Treatment Outcome

It has been reported that treatment with an angiotensin-converting enzyme (ACE) inhibitor is not adequate to suppress aldosterone, and we previously demonstrated that adding spironolactone to an ACE inhibitor may have beneficial effects on left ventricular hypertrophy (LVH) in selected patients with essential hypertension (EH). We have extended our previous short-term study, and addressed the relative long-term clinical effects of spironolactone and an ACE inhibitor in patients with EH who have LVH. Twenty patients with EH and concomitant LVH participated in this study. Subjects were treated with either an ACE inhibitor alone (group 1: 10 patients) or an ACE inhibitor plus spironolactone at the dose of 25 mg (group 2: 10 patients) for 60 weeks. The baseline clinical and echocardiographic characteristics of the two groups were similar. Final values of blood pressure were also similar between the two groups. The LV mass index (LVMI) decreased significantly in both groups, but the extent of reduction was significantly greater in group 2 at 60 weeks. The early peak to atrial peak filling velosities ratio (E/A ratio) was significantly increased to a similar extent in both groups. Serum procollagen type III amino-terminal peptide (PIIINP) was significantly decreased in group 2, but not in group 1. In group 2, there was a statistically significant correlation between the changes in LVMI and PIIINP. In conclusion, adding spironolactone to therapy with an ACE inhibitor for 60 weeks may have beneficial effects in patients with EH and concomitant LVH. Our study strongly suggests the possibility that attenuation of the effects of cardiac aldosterone in patients with EH by treatment with spironolactone and an ACE inhibitor may become a new goal for the prevention and regression of cardiac hypertrophy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Blood Pressure; Coronary Circulation; Diastole; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Indoles; Longitudinal Studies; Male; Middle Aged; Peptide Fragments; Procollagen; Spironolactone

Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular (LV) mass for comparable decreases in blood pressure (BP). However, some dihydropyridines, such as felodipine-extended release (ER), still increase sympathetic activity and may, therefore, be less effective in decreasing LV mass.. To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control (assessed by 24 h ambulatory BP monitoring) and sympathetic activity (assessed by plasma catecholamine concentrations).. Enalapril was started at 10 mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively, if the office BP remained 160/90 mmHg or greater at the end of the dosing interval. Evaluable echocardiograms were obtained for 116 patients at the end of the study (30 weeks of treatment).. On 24 h ambulatory BP monitoring, nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval, whereas felodipine-ER caused a more marked fall in BP during the day, and enalapril's effects diminished during the night and had disappeared by the morning. Only felodipine-ER significantly increased supine and standing plasma noradrenaline by more than 50% similarly after six, 18, and 30 weeks of treatment. In BP responders (decrease in systolic BP 10 mmHg or greater), enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2, whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus enalapril).. Once-daily dihydropyridines should not be regarded as one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits a better profile regarding 24 h BP control, sympathetic activation and regression of LV mass.

Topics: Antihypertensive Agents; Biomarkers; Blood Pressure; Data Interpretation, Statistical; Enalapril; Felodipine; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Norepinephrine; Placebo Effect; Single-Blind Method

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Time Factors

The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure, echocardiographically calculated left ventricular mass, renal function evaluated by glomerular filtration rate and quality of life. The renin-angiotensin-aldosterone system is of importance for cardiovascular growth. There is substantial experimental documentation in animals that the angiotensin II antagonist, losartan, decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload. However, data in humans is scarce. This is a 3-year, randomised, double-blind study with parallel group design in 50 patients with essential hypertension. The results show that both drugs reduced blood pressure equally effectively, and also left ventricular mass (P < 0.001). After 3 years of treatment glomerular filtration rate significantly increased with losartan (P < 0.005). Serum uric acid fell modestly although significantly, dose-dependent in losartan patients compared with an increase in enalapril patients. A fall in serum potassium from the pre-study period was observed in all patients. There was no difference between treatments in terms of patient satisfaction on quality of life. Both drugs have relatively similar hormonal and haemodynamic effect, with an excellent tolerability profile; they appear to induce comparable blood pressure falls in hypertensive patients in particular, therapy based on specific Ang II blockade may offer advantages in high risk hypertensives if left ventricular hypertrophy is present. Both enalapril and losartan, in improving the renal function attenuating the intrarenal effects of angiotensin II, might be able to reverse the pathophysiology of essential hypertensive kidney disease, and should be first-choice drugs in the treatment of essential hypertension.

Topics: Analysis of Variance; Antihypertensive Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Function Tests; Long-Term Care; Losartan; Male; Middle Aged; Probability; Radionuclide Imaging; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

In a single-center study, we compared to what extent changes in conventional and ambulatory blood pressure (BP) predicted regression of left ventricular mass (LVM) index in response to antihypertensive treatment in previously untreated and treated patients with sustained hypertension.. We enrolled 173 black African patients who, off treatment, had a daytime diastolic BP ranging from 90 to 114 mm Hg. Antihypertensive drugs were titrated and combined to reduce the daytime diastolic BP below 90 mm Hg. Echocardiograms were obtained at baseline and follow-up. Mean systolic/diastolic clinic BP, 24-hour BP, and LVM index were similar in previously untreated (n=64) and previously treated (n=109) patients and averaged 171/102 mm Hg, 151/97 mm Hg, and 118 g/m2, respectively. At 4 months, these values had decreased (P<0.001) by 26/12 mm Hg, 23/14 mm Hg, and 14 g/m2 in previously untreated patients and by 22/9 mm Hg, 21/13 mm Hg, and 19 g/m2 in previously treated patients. In the previously untreated patients, the regression in LVM index correlated to a similar degree (P=0.09) with the decreases in the conventional (r=0.34; P=0.005) and the 24-hour (r=0.26; P=0.04) systolic BP. In the previously treated patients, the corresponding correlations were 0.02 (P=0.82) and -0.10 (P=0.32), respectively. Compared with the 24-hour systolic BP, automated oscillometric measurements of systolic BP obtained at the clinic yielded similar results.. In previously untreated patients with sustained hypertension followed at a single center, reductions in clinic and ambulatory systolic pressure in response to antihypertensive treatment equally predicted the regression in LVM index.

Topics: Angiotensin-Converting Enzyme Inhibitors; Black People; Blood Pressure; Body Mass Index; Calcium Channel Blockers; Diastole; Diuretics; Echocardiography; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Methyldopa; Middle Aged; Nifedipine; Patient Compliance; Regression Analysis; South Africa; Systole; Verapamil

Left ventricular hypertrophy (LVH) commonly occurs in patients with end-stage renal disease (ESRD) and is an independent risk factor for cardiovascular events. Angiotensin II type 1 receptor (AT1-R) antagonists may be able to reverse LVH independent to the hypotensive effect in the ESRD setting. Thirty chronically hemodialyzed uremic patients with hypertension were randomly assigned to receive the AT1-R antagonist losartan (n = 10), the angiotensin-converting enzyme (ACD) inhibitor enalapril (n = 10), or calcium antagonist amlodipine (n = 10). Left ventricular mass (LVM) index was measured by echocardiography before and 6 months after treatment. The baseline demographic and clinical characteristics did not differ between the three groups. The mean baseline LVM index also did not differ in the three groups. After 6 months of treatment, losartan treatment significantly reduced the LVM index (-24.7 +/- 3.2%) than amlodipine (-10.5 +/- 5.2%) or enalapril (-11.2 +/- 4.1%) therapy. All three groups had a similar decrease in the mean blood pressure with treatment. The plasma angiotensin II concentration increased 5-fold with losartan treatment. In contrast, the plasma angiotension II concentration did not change with enalapril and only increased 2-fold with amlodipine. Thus, the present study indicates that losartan more effectively regresses LVH in patients with ESRD than do enalapril and amlodipine despite a comparable depressor effect between the three drugs.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Angiotensin II; Angiotensin Receptor Antagonists; Antihypertensive Agents; Echocardiography; Enalapril; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Losartan; Male; Middle Aged; Receptor, Angiotensin, Type 1; Renal Dialysis

This study sought to investigate the cardiac and renal effects of rigorous versus standard BP control on autosomal-dominant polycystic kidney disease (ADPKD). A prospective, randomized, 7-yr study was performed to examine the effect of rigorous (<120/80 mmHg) versus standard (135-140/85-90 mmHg) BP control on left ventricular mass index (LVMI) and kidney function in 75 hypertensive ADPKD patients with left ventricular hypertrophy. LVMI was measured by echocardiogram at baseline and at 1 and 7 yr. Renal function was assessed by measuring serum creatinine and 24-h creatinine clearance every 6 mo for 3 yr, then annually for an additional 4 yr. The baseline characteristics were comparable in the two groups. During the study, average mean arterial pressure was 90 +/- 5 mmHg for the rigorous group and 101 +/- 4 mmHg for the standard group (P < 0.0001). The LVMI decreased by 21% in the standard group and by 35% in the rigorous group. A mixed model longitudinal data analysis revealed that rigorous BP control was significantly more effective in decreasing LVMI (P < 0.01). There was no statistically significant difference in renal function between the two groups. In conclusion, left ventricular hypertrophy, a major cardiovascular risk factor, was decreased to a significantly greater extent by rigorous than standard BP control. This finding has particular clinical importance because cardiovascular complications are the most common cause of death in ADPKD patients.

Topics: Adult; Amlodipine; Antihypertensive Agents; Blood Pressure; Creatinine; Echocardiography; Enalapril; Female; Heart; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Longitudinal Studies; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Prospective Studies

Thiazides are recommended to initiate antihypertensive drug treatment in black subjects.. To test the efficacy of this recommendation in a South African black cohort.. Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen.. While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black People; Blood Pressure; Calcium Channel Blockers; Diastole; Diuretics; Drug Therapy, Combination; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Practice Guidelines as Topic; Proportional Hazards Models; Sodium Chloride Symporter Inhibitors; South Africa; Time Factors; Treatment Outcome; Vasodilator Agents; Verapamil

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

The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)).. An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS).. Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Diastole; Double-Blind Method; Electrocardiography; Enalapril; Female; Heart Ventricles; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Prospective Studies; Treatment Outcome

A study was carried out to evaluate the influence of antihypertensive treatment with combined low doses of enalapril plus isradipine (5+5 mg daily) compared with those of either drug at a higher dose level (10 mg daily) by double-blind, three-way crossover study (balanced Latin square design) in 102 subjects (mean age 51.9 +/- 7.42 years) with essential hypertension. Left ventricular mass and function were evaluated by M-B mode echocardiography, renal function by glomerular filtration rate (GFR) and by serum and 24-h urinary Na+ and K+ during wash-out period and after 24 weeks of treatment.. The supine blood pressure for subjects given placebo was 171/103 mmHg. After 24 weeks of treatment, systolic and diastolic supine blood pressure were significantly lower with 5 mg isradipine plus 5 mg enalapril (134/84 mmHg) than with 10 mg enalapril (137/84 mmHg) or with 10 mg isradipine (144/85 mmHg). Left ventricular posterior wall and septal thickness were significantly and similarly reduced in all groups. Left ventricular systolic and diastolic end diameters were not significantly changed. Left ventricular mass (LVM) was significantly reduced in E plus I group and enalapril group. GFR was not significantly altered. The 24-h urinary Na+ significantly increased with enalapril, more so than isradipine. The combination was tolerated better than either monotherapy. We observed no clinically significant changes in laboratory variables including blood lipoproteins.. The combination of isradipine plus enalapril reduced blood pressure more effectively and was better tolerated than other drug alone. All three groups showed similar changes in echocardiographic indices and no change in renal function.

Topics: Analysis of Variance; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Enalapril; Glomerular Filtration Rate; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male; Middle Aged; Statistics, Nonparametric

This study examined whether long-term therapy with an angiotensin-converting enzyme (ACE) inhibitor reduces excessive increases in left ventricular (LV) mass as well as volume in growing children with aortic regurgitation or mitral regurgitation.. The ACE inhibitor reduces volume overload and LV hypertrophy in adults with aortic or mitral regurgitation.. This study included 24 patients whose ages ranged from 0.3 to 16 years at entry to the study. On echocardiography, we measured LV size, systolic function and mass. After obtaining baseline data, patients were allocated into two groups. Twelve patients were given an ACE inhibitor (ACE inhibitor group), and 12 patients were not (control group). Echo parameters were again assessed after an average 3.4 years of follow-up.. Left ventricular parameters at baseline in the two groups were similar. The Z value of LV end-diastolic dimensions decreased from +0.82 +/- 0.55 to +0.57 +/- 0.58 in the ACE inhibitor group, whereas it increased from +0.73 +/- 0.85 to +1.14 +/- 1.04 in the control group (mean change -0.25 +/- 0.33 for the ACE inhibitor group vs. +0.42 +/- 0.48 for the control group, p = 0.0007). The mass normalized to growth also reduced from 221 +/- 93% to 149 +/- 44% of normal in the ACE inhibitor group and increased from 167 +/- 46% to 204 +/-59% of normal in the control group (mean change -72 +/- 89% of normal for the ACE inhibitor group vs. +37 +/- 35% of normal for the control group, p = 0.0007).. Long-term treatment with ACE inhibitors is effective in reducing not only LV volume overload but also LV hypertrophy in the hearts of growing children with LV volume overload.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Aortic Valve Insufficiency; Child; Child, Preschool; Cilazapril; Disease Progression; Echocardiography; Enalapril; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Infant; Mitral Valve Insufficiency; Myocardial Contraction; Observer Variation; Pilot Projects; Treatment Outcome; Ventricular Function, Left

To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses.. Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arterial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months.. The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m2): 141+/-3.9 to 123+/-3.6 in the enalapril group (p<0.05), from 147+/-3.8 to 133+/-2.8 in the losartan group (p<0.05), and from 146+/-3.0 to 116+/-4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5+/-5.0%) than in enalapril (12.4+/-3.2%) and the losartan (9.1+/-2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan.. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Topics: Adult; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Renin-Angiotensin System; Ventricular Function, Left

To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH).. The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence.. European hospitals, general practitioners and cardiologists.. Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients.. Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks.. LVMI variation in the perprotocol population.. Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months.. Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Male; Middle Aged

Left ventricular hypertrophy (LVH) is a clinical condition associated with an increased risk of vascular events. Several trials have been done to evaluate the action of different antihypertensive treatments on the regression of LVH IN HYPERTENSIVE PATIENTS. The efficacy of diuretics in the reduction of LVH is controversial. The LIVE study (Left Ventricular Hypertrophy Regression: Indapamide Versus Enalapril) is a European, prospective, double-blind, randomised, controlled trial aimed to compare the efficacy of indapamide 1.5 mg daily with that of enalapril 20 mg daily in the reduction of LVH in hypertensive patients (systolic blood pressure > 160 and < 210 mmHg) with LVH (left ventricular mass index 120 g/m2 in men and > 100 g/m2 in women) after 1 year of treatment. The assessment of LVH was done by echocardiography. A blind randomised reading of the echo recordings was performed at the end of the study by an independent Core Echocardiography Committee with three readers. Preliminary data are available from this trial. These data confirm the antihypertensive efficacy of indapamide and its efficacy in the reduction of left ventricular mass through a progressive action over 1 year.

Topics: Antihypertensive Agents; Clinical Trials as Topic; Enalapril; Humans; Hypertrophy, Left Ventricular; Indapamide; Remission Induction

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Topics: Acrylates; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Coronary Circulation; Double-Blind Method; Enalapril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Thiophenes

There is increasing evidence for important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Administration of aldosterone with excess salt produces both cardiac hypertrophy and interstitial cardiac fibrosis in rats, and concomitant administration of potassium canrenoate at a dose that only modestly lowers blood pressure completely blocks the cardiac effects of aldosterone. In the present study, we examined the effect on left ventricular hypertrophy of adding a low dose of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to an angiotensin-converting enzyme inhibitor (enalapril maleate) in patients with essential hypertension. Eighteen untreated patients with moderate to severe essential hypertension based on the WHO/ISH guidelines participated in this study. Subjects were treated with either an angiotensin-converting enzyme inhibitor alone (group I: 10 patients, 4 men and 6 women, mean age 56 +/- 18 yr) or an angiotensin-converting enzyme inhibitor plus spironolactone (group II: 8 patients, 3 men and 5 women, mean age 59 +/- 14 yr) for 9 mo. Left ventricular mass index, various echocardiographic variables, mean blood pressure, plasma renin activity, and plasma aldosterone concentration before treatment were similar in the two groups. Blood pressure of both groups decreased significantly and similarly after antihypertensive treatment (group I, 136 +/- 9/82 +/- 9 mmHg; group II, 133 +/- 9/85 +/- 10 mmHg). Left ventricular mass index also decreased significantly in both groups (group I, -10.2 +/- 7.1%; group II, -18.1 +/- 6.9%). The extent of reduction was significantly greater in the spironolactone group (group II) (p < 0.05 vs. group I). In group II patients, spironolactone did not cause any side effects during the observation period. We conclude that spironolactone may have beneficial effects on left ventricular hypertrophy in patients with essential hypertension who are receiving an angiotensin-converting enzyme inhibitor.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Follow-Up Studies; Heart Rate; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Radioimmunoassay; Renin; Spironolactone; Treatment Outcome

Hypertension occurs commonly and early in the natural history of autosomal dominant polycystic kidney disease (ADPKD), affecting both renal and patient outcome. Activation of the renin angiotensin aldosterone system due to cyst expansion and local renal ischaemia plays an important role in the development of ADPKD related hypertension and left ventricular hypertrophy (LVH), a known important risk factor for cardiovascular morbidity and mortality. The aim of this study was to investigate the effects of an angiotensin converting enzyme (ACE) inhibitor, enalapril, on renal function, blood pressure and LVH in hypertensive ADPKD patients.. Fourteen hypertensive ADPKD patients (11 men, 3 women; mean age: 40 years) were included in the study. All patients had LVH and creatinine clearance (Cer) greater than 50 ml/min/1.73 m2. The patients were followed for 7 years on enalapril therapy. The effects of enalapril on renal function, blood pressure and LVH were investigated.. Baseline measurements of mean arterial pressure (MAP), Ccr and left ventricular mass index (LVMI) were 110 +/- 2 mmHg, 84 +/- 6 ml/min/1.73 m2 and 146 +/- 4 g/m2, respectively. After one year of enalapril therapy there was a significant decrease in MAP (94 +/- 3 mmHg, P < 0.005) which remained stable until the end of the study at 7 years (94 +/- 1 mmHg, P < 0.005 vs baseline). There was also a significant decrease in LVMI (131 +/- 6 g/m2, P < 0.05) after year 1 which continued to decrease until the end of the study reaching 98 +/- 6 g/m2 (P < 0.01 vs year 1 and baseline). Although Ccr remained stable after year 1, a significant decrease was observed after 7 years of follow-up (59 +/- 6 ml/min, P < 0.001 vs year 1 and baseline).. ACE inhibition in hypertensive ADPKD patients provided long-term reversal of LVH in association with a mean 3.6 ml/min/year decline of Ccr. These preliminary results have potential important implications for cardiovascular and renal protection in ADPKD.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Prospective Studies

Abnormalities of left ventricular (LV) diastolic filling and stress-corrected midwall shortening (MWS) have been described in hypertensive patients with normal ejection fraction (EF). However, whether stress-corrected MWS parallels LV diastolic filling better than EF does remains uncertain. Blood pressure, body mass index, echocardiographic LV mass and LV geometry, EF and stress-corrected MWS, LV diastolic filling (peak E- and A-wave velocities, E-wave deceleration time, and atrial filling fraction) were evaluated in 212 hypertensive patients with LV hypertrophy enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement study. LV structure, geometry, as well as LV diastolic filling, were compared between patients with reduced EF (<55%, n = 39, 18%) and those with normal EF (>55%) as well as between patients with reduced stress-corrected MWS (<89.2%, n = 31, 15%) and those with normal stress-corrected MWS (>89.2%). Patients with reduced EF had higher LV mass, eccentric LV geometry, and higher heart rate than those with normal EF, although they did not differ in age, blood pressure, or body mass index. LV filling pattern was also similar in those 2 groups. Patients with reduced stress-corrected MWS had higher atrial filling fraction, body mass index, heart rate, LV mass, and concentric geometry than those with normal stress-corrected MWS. Atrial filling fraction was negatively associated with stress-corrected MWS, but not with EF in multivariate models, independently of age, gender, heart rate, and body mass index. Thus, in hypertensive patients with LV hypertrophy, abnormal LV diastolic filling is more closely related to impaired myocardial contractility than to LV chamber EF.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Volume; Diastole; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Contraction; Prospective Studies; Stroke Volume; Systole; Ventricular Function, Left

We examined the effect of long-term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immunological variables in patients with chronic congestive heart failure (CHF).. Immunological mediators are increasingly recognized to play a pathogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated.. Seventy-five patients (mean age 52 +/- 11 years) with CHF were randomized between low-(5 m g daily) and high-dose (40 mg daily) enalapril in a double-blind trial. Circulating levels of immunological parameters (i.e., proinflammatory cytokines, chemokines and adhesion molecules) were measured at baseline, at 10 weeks and at the end of the study (34 weeks).. All immunological parameters, except soluble interleukin (IL)-6 receptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 receptor increased (p < 0.05) during high-dose but not during low-dose enalapril therapy. Furthermore, IL-6 bioactivity decreased only during the high-dose (p < 0.001), resulting in a significant difference in change during treatment between the two dosage groups (p < 0.001). This decrease in IL-6 bioactivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other variables changed during treatment.. In patients with severe CHF, high-dose enalapril therapy is associated with a significant decrease in IL-6 activity. However, despite treatment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chemokine CCL2; Chronic Disease; Cytokines; Double-Blind Method; Echocardiography; Enalapril; Female; Heart Failure; Heart Septum; Humans; Hypertrophy, Left Ventricular; Immunoenzyme Techniques; Interleukin-1; Interleukin-6; Male; Methotrexate; Middle Aged; Neopterin; P-Selectin; Receptors, Interleukin-6; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Arterial pressure increases with age and is the most common chronic disease in the elderly, men and women alike. At present arterial hypertension is considered a social disease as it poses great health, economic and social problems.. A group of 50 patients of both sexes, between 66 and 83 years of age, suffering from essential arterial hypertension and treated with Enalapril administered at doses varying from 10 to 20 mg/day, for a period of 18 months, has been studied.. The results of this study showed that blood pressure values of almost all the patients treated normalised and left ventricular hypertrophy decreased in all patients with this complication.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Antihypertensive Agents; Blood Pressure; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Time Factors

This study was designed to evaluate in 45 hypertensive patients with left ventricular hypertrophy (LVH) the effects of a 6-month course with one of three different antihypertensive regimens (the calcium channel blocker isradipine, the angiotensin converting enzyme inhibitor spirapril in monotherapy, or a combination of the two drugs, n = 15 per group) on blood pressure, LVH regression, and various functional correlates of LVH. All three treatment modalities decreased significantly LV mass index by an average of 10%, although the combination had the greatest blood pressure-lowering effect and spirapril had the least, as assessed by office resting pressures, ambulatory monitoring, and isometric grip testing. There was no correlation between magnitude of blood pressure lowering and degree of LVH regression. The effects of treatment on pressor hormone profiles differed among groups, as spirapril tended to suppress angiotensin II and norepinephrine, whereas isradipine had opposite effects. Exercise tolerance was prolonged by all three regimens, but significantly more by the combination. All three regimens decreased significantly the double product by 10% to 15%. Indices of electrophysiologic stability calculated from analysis of ambulatory electrocardiogram exhibited significant improvement in several parameters such as QRS duration, presence of late potentials, and measures of heart rate variability, resulting in fewer episodes of simple or complex ventricular arrhythmia. We conclude that all three regimens produce significant LVH regression associated with improved functional capacity and electrical stability. These results reflect the sum of the differential hemodynamic and hormonal effects exerted by each treatment modality.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male

To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.. A double-blind randomized, placebo-controlled trial.. General practitioners referred patients to the trial physician.. The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks.. Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks.. The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography.. Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16).. These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nitrendipine

To test the feasibility and utility of instituting centralized echocardiographic quality control during a multicenter study of regression of left ventricular hypertrophy in hypertension.. The LIVE (Left Ventricular Hypertrophy: Indapamide Versus Enalapril) study is an ongoing multicenter, double-blind, controlled study of regression of echocardiographic left ventricular mass index in hypertensive patients with left ventricular hypertrophy (left ventricular mass indexes > 100 g/m2 for women and > 120 g/m2 for men) treated for 1 year with 1.5 mg indapamide sustained-release coated tablets versus 20 mg enalapril. A centralized evaluation committee has validated a prestudy sample echocardiogram from each center, and is now reviewing all videotapes recorded during this study for quality control; final results will be based on a further randomized blinded analysis by this centralized evaluation committee.. Since December 1994, 878 patients have been preselected (videoechocardiographic recordings sent for assessment), 645 selected (videoechocardiographic recordings validated), and 576 randomly allocated to treatment. After preliminary quality control, 27% (233) of baseline echocardiograms were rejected by our centralized evaluation committee, and 22% (142) of postinclusion echocardiographic measurements had to be repeated, mainly because they were of poor echogenic quality. Analysis of approved baseline echocardiograms for the first 274 randomly allocated patients with digitized data showed that there was a significant correlation between centralized evaluation committee and investigator calculations of left ventricular mass index (r = 0.76, P < 0.001), with consistently higher values for investigator calculations, independently of level of left ventricular mass index (correlation between difference and mean of investigator and centralized evaluation committee measurements, r = 0.08, P = 0.28). The mean difference was 8 +/- 20 g/m2 (P < 0.001).. Early results of the LIVE study quality control showed that real-time 'live', centralized echocardiographic reading was not only feasible, but also useful for avoiding unquantifiable echocardiograms and overestimation of left ventricular mass index. Thus, real-time, centralized echocardiographic quality control should be recommended for multicenter studies of regression of left ventricular hypertrophy.

Topics: Adult; Antihypertensive Agents; Double-Blind Method; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Male; Quality Control

Plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) are high in patients with hypertension and congestive heart failure. The present study examined changes in plasma ANP and BNP concentrations during 1 year of monotherapy with enalapril in elderly hypertensive patients with left ventricular (LV) hypertrophy. Eight elderly hypertensive patients with LV hypertrophy were treated with enalapril for 1 year, during which time serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of ANP and BNP. Enalapril maintained systolic and diastolic blood pressure in the normal range for over 1 year. Treatment significantly reduced posterior wall thickness at 6 months, and more so at 1 year, and tended to reduce septal wall thickness and LV mass index at 1 year. LV ejection fraction was slightly but significantly increased at 1 year. Plasma ANP and BNP, which were markedly elevated at study entry, both decreased after 1 year of enalapril. These results suggest that 1 year of treatment with enalapril caused both a modest regression of LV hypertrophy and a modest improvement in LV systolic function in our selected group of elderly hypertensive patients. The drug reduced elevated plasma ANP and BNP levels but did not alter BUN and serum creatinine levels. Enalapril appears to be useful for the treatment of elderly hypertensive patients with LV hypertrophy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Electrocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin; Systole; Ventricular Function, Left

Left ventricular hypertrophy is frequently noted in patients with moderate to severe chronic renal failure not requiring dialysis. Recently, several studies have shown reversal of myocardial hypertrophy in end-stage renal disease with long-term pharmacological control of blood pressure, but it is unclear whether left ventricular mass regresses or normalizes with antihypertensive treatment of patients with earlier stages of chronic renal failure.. Seventy-two undialysed patients with chronic renal failure, chronic mild-to-moderate hypertension, and left ventricular hypertrophy were randomly assigned in a prospective study to either the captopril (n = 36) or enalapril group (n = 36). Blood pressure measurements, echocardiographic and Doppler parameters were evaluated before treatment and at 6 and 12 months of therapy.. During follow-up, six patients developed side-effects including dry cough, taste disturbances, skin rash and gastric intolerance. In the captopril group there was a decrease in mean left ventricular mass index by 12% after 6 months of treatment, which decreased by 20% after 12 months treatment. For enalapril, the average reduction of myocardial mass after 6 months treatment was 14% and after 12 months treatment, the decrease was 19%. In both treatment groups there was significant improvement of left ventricular filling dynamics. No deterioration of left ventricular systolic function was observed.. Our results confirm that antihypertensive monotherapy with the ACE inhibitors, captopril and enalapril, in patients with chronic renal failure results in regression of left ventricular mass index associated with a significant improvement in the diastolic function of the left ventricle without a demonstrable deterioration in left ventricular systolic performance.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Diastole; Drug Tolerance; Enalapril; Female; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Single-Blind Method; Systole; Ventricular Function, Left

Topics: Adrenergic beta-Antagonists; Adult; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood; Calcium Channel Blockers; Diuretics; Double-Blind Method; Enalapril; Humans; Hydrochlorothiazide; Hypertrophy, Left Ventricular; Middle Aged; Nitrendipine; Single-Blind Method; Sodium Chloride Symporter Inhibitors

The present study was designed to evaluate the effects of early angiotensin converting enzyme (ACE) inhibition on left ventricular enlargement in patients with anterior wall infarction following reperfusion therapy.. Seventy-one consecutive patients with an anterior wall myocardial infarction were randomly allocated to enalapril (n = 36) or placebo (n = 35). All patients received either thrombolytic therapy (n = 46) or underwent primary coronary angioplasty (n = 25). Medication was started within 48 h admission to hospital and continued for 48 weeks. The process of left ventricular remodelling was assessed with two-dimensional echocardiography at 3 weeks and 1 year after the acute onset, and was related to the severity of the residual stenosis of the infarct-related artery.. Baseline left ventricular ejection fraction was 39.2% +/- 8.7%. During the study period left ventricular end-diastolic volume index increased from 48.2 +/- 9.9 ml.m-2 to 54.6 +/- 12.2 ml.m-2 at 3 weeks, and to 59.4 +/- 17.0 ml.m-2 after 1 year I control patients (P < 0.001). In the enalapril-treated patients, left ventricular end-diastolic volume index increased from 50.0 +/- 16.1 to 57.7 +/- 19.3 ml.m-2 at 3 weeks, and to 61.9 +/- 22.7 ml.m-2 after 1 year (P < 0.001). Both at 3 weeks and after 1 year, no overall differences in left ventricular volumes were observed between the enalapril and the placebo group (both ns). However, patients with a residual stenosis severity of > or = 70% in the infarct-related artery (n = 43) showed significant attenuation of remodelling by enalapril (n = 22) when compared to placebo (n = 21). In patients on enalapril, left ventricular end-diastolic volume index increased from 47.0 +/- 13.0 to 53.7 +/- 17.7 ml.m-2 compared to 48.0 +/- 9.6 to 60.3 +/- 16.3 ml.m-2 in control patients (P < 0.03). Also diastolic filling parameters were significantly improved in patients with > or = 70% residual stenosis.. In patients with an anterior wall infarction and a severe residual infarct-related coronary artery stenosis following reperfusion, treatment with enalapril prevents the process of left ventricular remodelling. As left ventricular dilatation is an early process we suggest that treatment with ACE inhibition should be started as soon as possible in this group of patients.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Disease; Double-Blind Method; Enalapril; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Prospective Studies; Ventricular Function, Left

The PRESERVE (Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement) study is designed to provide a definitive test of the ability of enalapril to achieve greater left ventricular (LV) mass reduction than nifedipine GITs (gastrointestinal treatment system) by a degree that would be prognostically meaningful on a population basis (10 g/m2). To achieve this goal, an ethnically diverse population of 480 men and women with essential hypertension and increased LV mass of screening echocardiography will be enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6 and 12 months' randomized therapy. Blinded readings of echocardiograms at a central laboratory will provide systematic information about treatment effects on LV structure, wall motion, and Doppler blood flow. The study power is at least 90% to test the primary hypotheses that enalapril will induce greater normalization of LV mass and diastolic filling than nifedipine. After the 1-year echocardiographic trial, the study population will be followed 3 more years to test the hypothesis that a reduction in LV mass, independent of blood pressure lowering, is associated with a reduction in the risk of morbid and fatal cardiovascular events.

Topics: Antihypertensive Agents; Double-Blind Method; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Prognosis; Research Design; Time Factors; Ventricular Function, Left

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arteries; Blood Pressure; Drug Combinations; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male; Prospective Studies; Vascular Resistance

To evaluate the antihypertensive efficacy at rest and under exercise, and the modifications induced on the left ventricular mass in patients treated with two different doses of a diuretic.. Fifty hypertensive males, mean age 51 years, received during nine months 50 mg/day of chlortalidone and thirteen 25 mg/day for the next nine months. Baseline tension control and echocardiogram and each three months after starting therapy during the two phases of the study were performed. Thickness of the interventricular septum and posterior left ventricular wall in mm, left ventricular mass index in g/m2 were determined.. The baseline septum was 15 +/- 3.3 mm, 14.6 +/- 3.1 mm at 9 months and 14.5 +/- 2.9 mm at 18 months, the posterior wall was 14.1 +/- 3.1 mm at baseline, 13.7 +/- 2.9 mm at 9 months and 13.6 +/- 2.9 mm at 18 months. The left ventricular mass index was 153 +/- 45 g/m2 at baseline, 146 +/- 36 g/m2 at 9 months and 144 +/- 39 g/m2 at 18 months. The antihypertensive efficacy at rest and under exertion was similar for the two doses of chlortalidone.. After nine months of therapy the two doses of chlortalidone (50 and 25 mg/day) failed in reducing left ventricular mass. However, the design of the study and the small number of subjects enrolled introduce several important limitations to both the interpretation of our results and conclusions.

Topics: Aged; Atenolol; Blood Pressure; Chi-Square Distribution; Chlorthalidone; Enalapril; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Prospective Studies; Remission Induction; Time Factors

Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension.. Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP).. ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related.. Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Treatment Outcome

To determine the effects of long-term treatment of essential hypertension with an angiotensin-converting enzyme inhibitor as regards arterial pressure at rest and during exercise, left ventricular mass and functional sequelae.. Twenty-six patients with previously untreated essential hypertension took enalapril 20 mg twice daily for 5 years. Cardiovascular parameters were determined by two-dimensionally guided M-mode echocardiography in a pre-treatment placebo phase, 8 weeks and 1, 3 and 5 years after the start of therapy, and 8 weeks after drugs were discontinued.. Therapy reduced resting arterial pressure from 156/105 to 128/84 mmHg (P < 0.001) and arterial pressure during exercise from 205/113 to 172/94 mmHg (P < 0.0011). After 1, 3 and 5 years' therapy, left ventricular mass index had decreased by 15, 28 and 39% respectively (P < 0.001 in each case). Eight weeks after treatment was halted, arterial pressure at rest and during exercise had returned to pre-treatment values, but decreased left ventricular mass was maintained. Left ventricular pump function had improved after 5 years' treatment, and this improvement was maintained during the 8 weeks without treatment.. Significant reductions in arterial pressure at rest and during exercise were achieved by 8 weeks' treatment with enalapril and maintained during 5 years' further treatment, while a marked reduction in left ventricular mass took place progressively throughout the 5 year period. Reduction of myocardial hypertrophy by enalapril appeared to be beneficial rather than detrimental to cardiac pump performance.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Long-Term Care; Male; Middle Aged; Ventricular Function, Left

Ventricular arrhythmias occur frequently in patients with hypertensive left ventricular (LV) hypertrophy and have been associated with increased incidence of sudden death. In this study, the effect of various antihypertensive medications on ventricular arrhythmias was evaluated in 31 hypertensive patients with moderate to severe LV hypertrophy. Patients were assessed at baseline (after 3 weeks of placebo treatment) and after treatment with each of 4 monotherapies: diltiazem 120 or 240 mg/day, metoprolol 100 or 200 mg/day, enalapril 10 or 20 mg/day and hydrochlorothiazide 50 or 100 mg/day. Each drug therapy was administered for 4 weeks. The sequence of each treatment was determined at random. Echocardiographic measurements and electrocardiograms were obtained only at baseline. Biochemical measurements and 48-hour Holter monitoring were obtained at baseline and at the end of each treatment. All treatments resulted in a significant but similar decrease in blood pressure. In the group as a whole diltiazem decreased ventricular premature complexes (VPCs) by 65% (p < 0.05) and metoprolol by 52% (p = 0.07). Enalapril and hydrochlorothiazide had no effect. In 12 patients with > or = 5 VPCs/hour at baseline, diltiazem and metoprolol decreased VPCs by 66% (p < 0.05). It is concluded that in hypertensive patients with moderate to severe LV hypertrophy, both diltiazem and metoprolol significantly reduce VPCs.

Topics: Analysis of Variance; Antihypertensive Agents; Cardiac Complexes, Premature; Diltiazem; Echocardiography; Electrocardiography, Ambulatory; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Metoprolol; Regression Analysis

The aim of the present study was to evaluate the effect of dihydropyridine calcium antagonist isradipine on left ventricular (LV) structure and function in patients with essential hypertension. Cuff blood pressure and Doppler echocardiographic variables were assessed in 26 patients with mild to moderate hypertension (diastolic blood pressure range 95-110 mmHg) before and after 12 weeks of therapy with either isradipine 5 mg daily or enalapril 20 mg daily. The study was of double-blind, parallel design, with a placebo run-in period of 15 days. Three subjects withdrew from isradipine treatment because of flushing and 2 from enalapril treatment due to cough before completing the study. Both drugs significantly reduced cuff systolic and diastolic blood pressure (p < 0.001) without affecting heart rate. By virtue of the decrease in both septal wall (p < 0.01) and posterior wall thicknesses (p < 0.05), isradipine treatment produced a significant reduction in LV mass adjusted for height (p < 0.001) in comparison with placebo; also LV end-systolic dimension showed a slight decrease (p < 0.05). Enalapril induced a similar reduction in LV end-systolic dimension (p < 0.05) but the changes of wall thickness and LV mass did not reach statistical significance. In conclusion, our results indicate that isradipine treatment improves LV systolic function and causes a significant reduction in LV mass. This reduction is observed early in the course of antihypertensive treatment and is effective in both patients with and without LV hypertrophy.

Topics: Antihypertensive Agents; Blood Pressure; Double-Blind Method; Echocardiography, Doppler; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male; Middle Aged; Ventricular Function, Left

To assess the long-term course of regression of left ventricular hypertrophy (LVH) and haemodynamic changes during spirapril treatment, 11 male hypertensive patients with a left ventricular mass (LVM) > 240 g and a mean age of 48 (range 41-60) years were followed-up with echo-Doppler examinations for 36 months. The initial spirapril dose was 6 or 12 mg once daily, which was titrated to a minimum of 3 mg and a maximum of 24 mg to keep diastolic blood pressure (DBP) < or = to 95 mmHg. Patient compliance based on tablet counts was 98% (range 95-100%). The mean spirapril dose was 9 +/- 6 mg at 3 months, 9 +/- 6 mg at 12 months, and 15 +/- 9 mg at 36 months. Blood pressure was reduced from 161 +/- 20/107 +/- 6 mmHg at baseline to 137 +/- 11/89 +/- 6 mmHg at 3 months (p < 0.001), 141 +/- 20/89 +/- 4 mmHg at 12 months and 135 +/- 11/87 +/- 6 mmHg at 36 months. The respective values for LVM at baseline and at 3, 12 and 36 months were 340 +/- 71 g, 305 +/- 61 g (p < 0.05 vs baseline), 303 +/- 88 g and 298 +/- 94 g. Cardiac output did not change whereas systemic arteriolar resistance (SAR) was significantly reduced after 3 and 36 months (p < 0.01). Thus, the regression of LVH with spirapril was 10% of LVM at 3 months, 11% at 12 months, and 12% at 36 months. These changes were mainly related to a reduction of LV posterior wall thickness and SAR.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Echocardiography, Doppler; Enalapril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Single-Blind Method

The effects of angiotensin converting enzyme (ACE) inhibitors on mortality following acute myocardial infarction (MI) has recently been studied in several clinical trials. The rationale for the use of these drugs following an injury to the myocardium is largely based on their ability to attenuate left ventricular volume expansion and modulate neurohormonal activation. Left ventricular dilatation following MI is due to complex structural changes in the infarcted myocardium as well as alterations in the non-infarcted contractile myocardium. The magnitude of this remodelling is associated with adverse prognosis. Neurohormonal systems are activated in the early phase of acute MI. Prolonged neurohormonal activation mainly occurs among patients with marked left ventricular dysfunction. The CONSENSUS II trial examined the effects on mortality of the ACE inhibitor enalapril, when initiated within 24 h from the onset of the infarct and continued for 6 months. There were 6090 patients randomly assigned to placebo (n = 3046) or enalapril (n = 3044). At the end of the trial, 598 patients had died: 286 (9.4%) in the placebo group and 312 (10.2%) in the enalapril group (P = 0.26). These results are in contrast to some other studies in which mortality was reduced by ACE inhibitor therapy post-MI. It is considered likely that the positive effects of ACE inhibitors following MI are confined mainly to patients with marked left ventricular dysfunction and prolonged neurohormonal activation.

Topics: Aged; Double-Blind Method; Enalapril; Female; Humans; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Sympathetic Nervous System; Time Factors

The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on regression of left ventricular hypertrophy (LVH), an independent predictor of poor prognosis in hypertension, was compared by echocardiography to that of nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100 mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind studies in 151 hypertensive patients with a diastolic blood pressure between 95 and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux). Patients were randomized to IND or comparator following a 2-week washout (1 month in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2) were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p < 0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n = 19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p < 0.001) vs. 170.4 +/- 6.6 and 148.2 +/- 6.2 (p < 0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p < 0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p < 0.001); IND (n = 17) vs. ATL (n = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p < 0.001) vs. 156.7 +/- 8.4 and 142.9 +/- 10.3 (p < 0.01). All drugs significantly reduced diastolic blood pressure, and all except HCTZ induced a significant and similar reduction in left ventricular mass.

Topics: Adult; Aged; Atenolol; Blood Pressure; Double-Blind Method; Enalapril; Female; France; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Italy; Male; Middle Aged; Nifedipine; United Kingdom

The influence of a 3-month antihypertensive treatment on cardiac structure and renal function was assessed in patients with uncomplicated essential hypertension randomly allocated to treatment by the nonselective beta-blocker tertatolol or the angiotensin-converting enzyme inhibitor enalapril. Both tertatolol and enalapril treatments were associated with a similar decrease in mean arterial pressure (-26 +/- 6 and -15 +/- 2 mm Hg, respectively, both p < 0.05 in comparison with baseline values) and left ventricular mass (echocardiography: -48 +/- 17 vs. -18 +/- 6 g) but no change in glomerular filtration rate (DTPA clearance). Renal vascular resistance decreased similarly in both groups. Urinary albumin excretion was not significantly modified in either group. These results indicate that a consistent reduction in arterial pressure by either treatment was associated with a proportional change in left ventricular geometry and no alteration in renal function.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Echocardiography; Enalapril; Female; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Function Tests; Male; Middle Aged; Propanolamines; Thiophenes; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Enalapril; Exercise; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Indoles; Male

This trial investigated the effect of enalapril, administered early, on left ventricular (LV) volumes after myocardial infarction. Four hundred twenty-eight patients included in the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) were examined with echocardiography within 5 days, at 1 month and at 6 months after myocardial infarction. Enalaprilat (1 mg) or placebo infusion was initiated within 24 hours after infarction, followed by oral treatment to a target dose of 20 mg/day. A significant attenuation of LV dilatation was noted at 1 month in patients treated with enalapril compared with those receiving placebo. Changes in LV end-diastolic volume indexes during the first month were (mean +/- SEM) 5.7 +/- 1.0 ml/m2 for the placebo group and 1.9 +/- 0.8 ml/m2 for the enalapril group (p < 0.02). Changes in LV end-systolic volume indexes were 3.1 +/- 0.8 and 0.5 +/- 0.6 ml/m2, respectively (p < 0.02). The between-group difference was most marked in patients with anterior wall infarction (p < 0.005). Volume changes beyond the first month were similar in both groups but the differences observed at 1 month were maintained. The larger volumes in the placebo versus enalapril group were significant or borderline significant at 1 and 6 months. Thus, enalapril treatment initiated early after myocardial infarction and continued for 6 months can attenuate LV dilatation during the first month resulting in smaller LV volumes after 1 and 6 months.

Topics: Aged; Drug Administration Schedule; Enalapril; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Myocardial Infarction; Stroke Volume

Primarily to investigate the long-term effects of antihypertensive therapy on left ventricular morphology in non-malignant essential hypertension and in particular to compare an angiotensin converting enzyme inhibitor and a diuretic in this respect.. Previously untreated males aged 20-65 years with diastolic blood pressure > or = 95 mmHg during a 4- to 6-week placebo period were randomly assigned to double-blind treatment with enalapril or hydrochlorothiazide.. Indirect and intra-arterial blood pressure, echocardiography, apex cardiography, carotid pulse tracing and phonocardiography.. Left ventricular mass (LVM) was significantly correlated with intra-arterial blood pressure at baseline. During long-term treatment (14-18 months) blood pressure decreased significantly in both treatment groups (indirectly and intra-arterially), at rest and during dynamic exercise. No significant differences in blood pressure response were seen between the two therapeutic alternatives. LVM decreased progressively and significantly on enalapril after 18 months of monotherapy and decreased non-significantly on hydrochlorothiazide after 14 months of monotherapy. The difference in effect between treatments was significant in a stepwise regression analysis taking change in blood pressure into account. The relationship between the reductions in LVM and blood pressure were significant for enalapril but not for hydrochlorothiazide. Neither therapy affected left ventricular diastolic or systolic diameters significantly, but enalapril reduced posterior wall thickness and interventricular septal thickness significantly, and improved left ventricular distensibility significantly. Neither therapy had any negative effects on systolic function, although hydrochlorothiazide decreased left ventricular ejection time index significantly.. Enalapril was significantly more effective than hydrochlorothiazide in reversing left ventricular hypertrophy without negatively affecting left ventricular function.

Topics: Adult; Aged; Blood Pressure; Double-Blind Method; Echocardiography; Enalapril; Heart; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Ventricular Function, Left

Eye-ground-photos were taken in twenty-eight previously untreated men with mild to moderate essential hypertension. The same eye was evaluated before and after 26 weeks of double-blind treatment with Enalapril or Hydrochlorothiazide. The vascular changes were assessed by using a more elaborate and refined grading than the Keith-Wagener-Barker scale. All photos were examined by the same observer without knowledge of blood pressure, type of treatment or the order in which the photos had been taken. There were significant positive correlations between the vascular alterations in the retina in the untreated state and left ventricular wall thickness (echocardiography), minimal vascular resistance in the calf (plethysmography) and blood pressure respectively. Treatment with Enalapril decreased the reflection of the retinal arterial wall significantly and reduced the narrowing of arteries and arterio-venous crossing phenomena non-significantly. Hydrochlorothiazide did not affect any of the retinal vascular changes. It can be concluded that this relatively simple technique of evaluating eye-ground-photos with a new grading scale, when used in non-malignant hypertension, gives a useful assessment of the degree of hypertensive target organ damage in the retina as well as in other important target organs, i.e. the heart and vascular beds. In addition, Enalapril positively affects hypertensive retinopathy in contrast to Hydrochlorothiazide, reflecting what happens to structural cardiovascular changes in the rest of the body.

Topics: Adult; Antihypertensive Agents; Arterioles; Child; Double-Blind Method; Echocardiography; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Photography; Prospective Studies; Retinal Vessels

Both beta-blockers and angiotensin-converting enzyme (ACE) inhibitors have been shown to cause left ventricular hypertrophy regression in hypertensive patients. So far, no study allowed a true comparison of these drugs in this regard. Therefore, 56 hypertensive patients (38 newly recognized and 18 without any antihypertensive drugs for more than 2 months, mean of 9.5+/-14 months) were randomized to enalapril (En, n = 30) or a beta-blocker, bisoprolol (Bi, n = 26), once daily and underwent before and after 2 and 6 months on treatment (a) office and 24-h ambulatory monitoring of BP, (b) M-mode echo assessment of left ventricular mass (LVM) index and fractional shortening (FS), and (c) Doppler evaluation of left ventricular filling. All recordings were read blindly by two observers. The intraobserver coefficient of variation of LVM was 9%. After 6 months, office BP (146+/-18/90+/-10 vs. 170+/-14/104+/-8 mm Hg) and 24-h BP(120+/-17/77+/-9 vs. 138+/-15/90+/-9 mm Hg) were similarly reduced with both drugs. The LVM index was significantly reduced (p < 0.001) (Bi, 11%; En, 7%) and FS was unchanged. The early to late diastolic left ventricular flow ratio (E/A) was increased with bisoprolol (1.06+/-0.29 vs. 0.85+/-0.17, p < 0.0001) but not with enalapril (0.95+/-0.24 vs. 0.88+/-0.34), but this was mainly due to heart rate reduction with bisoprolol. We found no correlation between the reductions in 24-h BP and in LVM index. Bisoprolol and enalapril were similarly effective in lowering blood pressure (BP) in the office and during 24-h monitoring and in reducing the left ventricular mass index in hypertensive patients.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chi-Square Distribution; Enalapril; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Single-Blind Method; Ventricular Function, Left

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Calcitriol; Cardiotonic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Fibrosis; Hyperparathyroidism; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; Myocardial Contraction; Myocardium; Nephrectomy; Parathyroid Hormone; Rats, Sprague-Dawley; Receptors, Calcitriol; Recovery of Function; Renal Insufficiency, Chronic; Stroke Volume; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

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

Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-ω-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n = 36) or tap water (n = 36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (P<0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11 ± 10.0 mm(2) vs. Enal+L: 4 ± 4.4 mm(2)), interstitial fibrosis (Con+L: 3 ± 2.5% vs. Enal+L: 1 ± 1.0%) and tissue macrophages (Con+L: 12 ± 9 mm(2) vs. Enal+L: 5 ± 3.6 mm(2)). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cell Proliferation; Creatinine; Disease Models, Animal; Enalapril; Fibrosis; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; NG-Nitroarginine Methyl Ester; Rats; Rats, Inbred SHR; Urea

The objective of this study was to establish whether 1) hyperactivity of renin-angiotensin-aldosterone system (RAAS) produces apoptosis in early stages of cardiac disease; and 2) Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is involved in these apoptotic events. Two models of hypertrophy were used at an early stage of cardiac disease: spontaneously hypertensive rats (SHR) and isoproterenol-treated rats (Iso-rats). At 4 mo, SHR showed blood pressure, aldosterone serum levels, used as RAAS activity index, and left ventricular mass index, used as hypertrophy index, above control values by 84.2 ± 2.6 mmHg, 211.2 ± 25.8%, and 8.6 ± 1.1 mg/mm, respectively. There was also an increase in apoptotis (Bax-to-Bcl-2 ratio and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells) associated with an enhancement of CaMKII activity with respect to age-matched controls (phosphorylated-CaMKII, 98.7 ± 14.1 above control). Similar results were observed in 4-mo-old Iso-rats. Cardiac function studied by echocardiography remained unaltered in all groups. Enalapril treatment significantly prevented hypertrophy, apoptosis, and CaMKII activity. Moreover, intracellular Ca(2+) handling in isolated myocytes was similar between SHR, Iso-rats, and their aged-matched controls. However, SHR and Iso-rats showed a significant increase in superoxide anion generation (lucigenin) and lipid peroxidation (thiobarbituric acid reactive substance). In transgenic mice with targeted cardiomyocyte expression of a CaMKII inhibitory peptide (AC3-I) or a scrambled control peptide (AC3-C), Iso treatment increased thiobarbituric acid reactive substance in both strains, whereas it increased CaMKII activity and apoptosis only in AC3-C mice. Endogenous increases in RAAS activity induce ROS and CaMKII-dependent apoptosis in vivo. CaMKII activation could not be associated with intracellular Ca(2+) increments and was directly related to the increase in oxidative stress.

Topics: Aldosterone; Animals; Apoptosis; Blood Pressure; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Enalapril; Heart; Hypertrophy, Left Ventricular; Isoproterenol; Lipid Peroxidation; Male; Mice; Mice, Transgenic; Myocytes, Cardiac; Oxidative Stress; Peptides; Rats; Rats, Inbred SHR; Rats, Wistar; Reactive Oxygen Species; Renin-Angiotensin System; Superoxides

Left ventricular hypertrophy (LVH) is the most frequent cardiac complication in chronic renal disease. Previous studies implicate elevated serum phosphorus as a risk factor for LVH.. We treated 5/6 nephrectomized rats with enalapril or enalapril + sevelamer carbonate for 4 months to determine if sevelamer carbonate had an additional beneficial effect on the development of LVH and uremia-induced left ventricle (LV) remodeling.. Uremia increased LV weight and cardiomyocyte size. Enalapril and enalapril + sevelamer blunted the increase in left ventricular weight. Only enalapril + sevelamer diminished the increase in cardiomyocyte size. Uremia increased cyclin D2 and PCNA and decreased p27 protein expression in the heart. Enalapril + sevelamer diminished the decrease in p27 expression caused by uremia. Uremia increased Ki67-positive and phosphohistone H(3)-positive interstitial cells. This was not seen in cardiomyocytes. Multivariable regression analysis showed that increased phosphorus was an independent risk factor for both increased LV weight and cardiomyocyte size.. These data suggest left ventricular remodeling consists of cardiomyocyte hypertrophy and interstitial cell proliferation, but not cardiomyocyte proliferation. p27 and cyclin D2 may play important roles in the development of LVH. In addition, phosphorus can be an independent risk factor for the development of LVH.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cell Cycle Proteins; Enalapril; Female; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Polyamines; Rats; Rats, Sprague-Dawley; Sevelamer; Uremia

Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown.. To determine whether angiotensin-(1-9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin-angiotensin system.. The administration of angiotensin-(1-9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1-9) was not modified with the simultaneous administration of the angiotensin-(1-7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 micromol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1-9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1-9) levels by several folds. Angiotensin-(1-9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction.. Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Bradykinin; Cardiomegaly; Cell Enlargement; Cells, Cultured; Enalapril; Humans; Hypertrophy, Left Ventricular; In Vitro Techniques; Insulin-Like Growth Factor I; Male; Myocardial Infarction; Myocytes, Cardiac; Norepinephrine; Peptide Fragments; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Tetrazoles; Ventricular Function, Left

The prevalence of left ventricular hypertrophy (LVH) is frequent in patients with end-stage renal disease following chronic renal failure (CRF). We investigated the therapeutic efficacy of curcumin, the principal curcuminoid of the Indian curry spice turmeric, in attenuation of LVH and sought to delineate the associated signaling pathways in blunting the hypertrophic response in nephrectomized rats. Adult Sprague-Dawley rats underwent nephrectomy (Nx) by removal of 5/6 of the kidneys. Four groups were studied for 7 wk: 1) control (sham), 2) Nx, 3) Nx + curcumin (150 mg/kg bid), and 4) Nx + enalapril (15 mg/kg bid) as positive control. Subtotal nephrectomy caused renal dysfunction, as evidenced by a gradual increase in proteinuria and elevation in blood urea nitrogen and plasma creatinine. Nx rats showed a significant hypertrophic response and increased diameter of inferior vena cava at inspiration, which was inhibited by treatment with curcumin or enalapril. Moreover, the Nx rats demonstrated changes in the signaling molecules critically involved in the hypertrophic response. These include increased glycogen synthase kinase-3β phosphorylation, β-catenin expression, calcineurin, phosphorylated (p) nuclear factor of activated T cells, pERK, and p-cAMP-dependent kinase. Both curcumin and enalapril variably but effectively deactivated these pathways. Curcumin attenuates cardiac hypertrophy and remodeling in nephrectomized rats through deactivation of multiple hypertrophic signaling pathways. Considering the safety of curcumin, these studies should facilitate future clinical trials in suppressing hypertrophy in patients with CRF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Blood Urea Nitrogen; Calcineurin; Creatinine; Curcumin; Disease Models, Animal; Enalapril; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Nephrectomy; NFATC Transcription Factors; Rats; Rats, Sprague-Dawley; Ventricular Remodeling

Topics: Acute Kidney Injury; Antihypertensive Agents; Biopsy; Child; Diagnosis, Differential; Enalapril; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Kidney; Propranolol; Purpura, Thrombotic Thrombocytopenic; Radionuclide Imaging; Renal Dialysis; Severity of Illness Index; Technetium Tc 99m Dimercaptosuccinic Acid; Time Factors; Treatment Outcome

Controlling hypertension by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), mechanisms that inhibit later pathway steps in the renin-angiotensin system (RAS), have clinically afforded protection against cardiac and renal disease.. In order to determine if blocking the RAS rate-limiting step of angiotensin II generation via renin inhibition could afford similar end organ protection in a human-relevant preclinical model, this study investigated the cardiac and renal effects of a nonpeptide, piperidine renin inhibitor (RI; 100 mg/kg/day PO) in double transgenic mice (dTGM) which express both human renin and angiotensinogen genes. RI was compared to the ARB, candesartan (3 mg/kg/day PO), and to the ACEI, enalapril (60 mg/kg/day PO) in a 4-week dosing paradigm. These doses of RI, ACEI and ARB were previously found to normalize mean blood pressure (MBP) to 110 + 3, 109 + 7 and 107 + 6 mmHg, respectively, after 1 day of treatment.. In the dTGM, PRA, plasma aldosterone, GFR, microalbuminuria and left ventricular free wall thickness (LVH) were higher than in the wild type C57BL/6 mice. Microalbuminuria and LVH were significantly reduced by 93% and 9% for the RI, 83% and 13% for enalapril and 73% and 6% for candesartan, respectively. PRA and aldosterone were reduced by the RI 56% and 23%, respectively. These results suggest that the RI provides protection against cardiac and renal disease, similar to ARB and ACEI.

Topics: Administration, Oral; Albuminuria; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Cardiotonic Agents; Drug Administration Schedule; Enalapril; Female; Glomerular Filtration Rate; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Structure; Piperidines; Quinolines; Renin; Renin-Angiotensin System; Tetrazoles; Time Factors; Ultrasonography

Left ventricular hypertrophy (LVH) is a complication of hypertension that has received great attention in the adult population. Large-scale randomized control studies in adults have demonstrated that LVH regresses in response to pharmacologic intervention. While it is known that LVH occurs as a complication of hypertension in the pediatric population, few studies have focused on its regression with pharmacological intervention. We report on three cases of hypertension-induced LVH in the pediatric population and its regression after treatment with antihypertensive medications. This report brings to light the need for larger, prospective studies on the incidence, natural history, and treatment of LVH associated with hypertension in the pediatric population.

Topics: Adolescent; Antihypertensive Agents; Child; Disease Progression; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Remission Induction

Topics: Aortic Valve Insufficiency; Enalapril; Humans; Hypertrophy, Left Ventricular; Nifedipine; Vasodilator Agents

Although blood pressure is considered the major determinant of left ventricular hypertrophy in hypertension, genetic variability is increasingly being considered among the factors influencing this complication. beta(2)-Adrenergic receptors (beta(2)ARs) are up-regulated in hypertension and largely polymorphic within the human population. Recently, we have shown that the Glu27 beta(2)AR variant is strongly associated with cardiac hypertrophy in hypertension. The objective of this study is to verify whether this polymorphism also affects hypertrophy regression in response to antihypertensive therapy.. In a prospective follow-up study we screened 970 hypertensive patients of Caucasian descent for the Gly16Arg, Gln27Glu, and Thr164Ile beta(2)AR polymorphisms and left ventricular echocardiographic hypertrophy and assigned selected patients to enalapril or atenolol to assess left ventricular hypertrophy regression after 2-year follow-up. Results were stratified according to treatment and the Glu27Gln polymorphism of the beta(2)AR. In cells with stable overexpression of the Glu27 or Gln27 variant of beta(2)AR, we also explored the implications of this polymorphism on hypertrophy-related intracellular signal transduction.. Among hypertensive patients, the Gly16 allele was found in 63% of patients and the Glu27 allele was found in 40.6%. Both polymorphisms were in linkage disequilibrium, as expected. Four hundred forty-one hypertrophic hypertensive patients completed the 2-year follow-up. At baseline, patients carrying at least 1 allele of the Glu27 variant presented with a larger cardiac size despite similar blood pressure levels (142.9 +/- 22.5 g/m(2) in Glu27 carriers versus 138.2 +/- 18.4 g/m(2) in Gln27 carriers, P < .02). Blood pressure normalization was achieved by both drugs. At follow-up, compared with the Gln27 patients, the Glu27 patients showed a larger reduction in hypertrophy when treated with enalapril (percent change in left ventricular mass, -6.3% +/- 7.7% in Glu27 carriers versus -2.18% +/- 7.9% in Gln27 carriers; P < .05) but not with atenolol therapy (-2.8% +/- 8.9% in Glu27 carriers versus -2.4% +/- 8.8% in Gln27 carriers, P = not significant). In in vitro studies the activation of p38 and extracellular signal-regulated kinase (ERK-) 1/2 (data not shown) and the activity of the atrial natriuretic factor (ANF) promoter after isoproterenol (INN, isoprenaline) stimulation were larger in Glu27 beta(2)AR overexpressing cells than in Gln27 beta(2)AR overexpressing cells (fold difference compared with unstimulated cells, 9.7 +/- 2.9 for Glu27 beta(2)AR versus 4.2 +/- 0.3 for Gln27 beta(2)AR; P < .05).. The Glu27 variant of beta(2)AR enhances hypertension-induced left ventricular hypertrophy. In these patients angiotensin-converting enzyme inhibitors are more efficient than beta-blockers in reducing cardiac size.

Topics: Antihypertensive Agents; Atenolol; Enalapril; Female; Genotype; Heterozygote; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Receptors, Adrenergic, beta-2; Signal Transduction

The objective was to assess the cardiac effects of growth hormone (GH) therapy. Anthracycline-treated childhood cancer survivors frequently have reduced left ventricular (LV) wall thickness and contractility, and GH therapy may affect these factors.. We examined serial cardiac findings for 34 anthracycline-treated childhood cancer survivors with several years of GH therapy and baseline cardiac z scores similar to those of a comparison group (86 similar cancer survivors without GH therapy).. LV contractility was decreased among GH-treated patients before, during, and after GH therapy (-1.08 SD below the age-adjusted population mean before therapy and -1.88 SD 4 years after therapy ceased, with each value depressed below normal). Contractility was higher in the control group than in the GH-treated group, with this difference being nearly significant. The GH-treated children had thinner LV walls before GH therapy (-1.38 SD). Wall thickness increased during GH therapy (from -1.38 SD to -1.09 SD after 3 years of GH therapy), but the effect was lost shortly after GH therapy ended and thickness diminished over time (-1.50 SD at 1 year after therapy and -1.96 SD at 4 years). During GH therapy, the wall thickness for the GH-treated group was greater than that for the control group; however, by 4 years after therapy, there was no difference between the GH-treated group and the control group.. GH therapy among anthracycline-treated survivors of childhood cancer increased LV wall thickness, but the effect was lost after therapy was discontinued. The therapy did not affect the progressive LV dysfunction.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Body Height; Cardiovascular Agents; Child; Child, Preschool; Enalapril; Female; Heart Ventricles; Hemodynamics; Human Growth Hormone; Humans; Hypertrophy, Left Ventricular; Hypopituitarism; Infant; Male; Myocardial Contraction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Ultrasonography; Ventricular Dysfunction, Left

To investigate the effect of Tianma Gouteng recipe (TGR) on interfering left ventricular (LV) and aortic hypertrophy and tissue angiotensin II (Ang II) in rats with renovascular hypertension.. The animal model of renovascular hypertension was used in this experiment. Hypertensive rats were randomly allocated into model group, Enalapril group and TGR group, and the drugs were used for 6 weeks continuously. During this period, the blood pressure of rats was measured every two weeks. After rats were sacrificed, the wet weight, tissue Ang II level of LV and aorta, and the cardiac index were measured.. One week after renovascular stenosis, the systolic blood pressure (SPS) of model group was increased by 37.4 mmHg, and 7 weeks after stenosis, the LV and aortic hypertrophy was obvious increased, meanwhile, tissue Ang II of LV and aorta was raised markedly (P < 0.01). Contrasting with the model group, blood pressure was reduced and the morphological index was improved in Enalapril group respectively (P < 0.05 or P < 0.01); the wet weight of LV and aorta were reduced, the morphological index was improved, the rise of Ang II in tissue was suppressed, in TGR group significantly.. TGR can attenuate myocardial and aorta hypertrophy induced by renovascular hypertension, and suppress the rise of Ang II in tissue significantly. This suggests that TGR has the effects on interfering LV and aortic hypertrophy by an independent-antihypertensive way.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Aorta; Drug Combinations; Drugs, Chinese Herbal; Enalapril; Gastrodia; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Male; Plants, Medicinal; Random Allocation; Rats; Rats, Wistar; Uncaria

Renin-angiotensin system inhibitors transiently induce apoptosis at the onset of cardiac hypertrophy regression in spontaneously hypertensive rats (SHRs). The focus of this study is to evaluate the cell selectivity of this response.. SHRs were treated with valsartan or enalapril (30 mg kg(-1) day(-1)) or placebo for 1 to 4 weeks. Stereological and morphological data were obtained from immunohistological analyses. Apoptosis was quantified by DEVDase (caspase-3-like) activity assay and immunoblot analysis of apoptosis-regulatory proteins (Bax and Bcl-2). Identification of the apoptotic cell type was conducted using in situ TUNEL labeling, in conjunction with alpha-sarcomeric actin or lectin immunoreactivity as markers for cardiomyocytes and endothelial cells, respectively.. Stereological analysis of the left ventricle revealed significant non-cardiomyocyte hyperplasia in placebo-treated SHRs (239+/-29x10(6) nuclei) as compared to untreated age-matched normotensive Wistar-Kyoto (WKY) rats (107+/-12x10(6)). In contrast, the number of cardiomyocyte nuclei was comparable between untreated SHRs (48+/-4x10(6)) and WKY rats. After 4 weeks of valsartan or enalapril treatment, SHRs showed significant reductions in systolic blood pressure (>28%), left ventricular hypertrophy (>9%) and cardiomyocyte cross-sectional area (>17%). Moreover, these treatments abolished non-cardiomyocyte hyperplasia in SHR left ventricle without affecting cardiomyocyte number, capillary density or number of capillary per cardiomyocyte nucleus. As a mechanism of cell deletion consistent with apoptosis induction, ventricles showed increased caspase-3 activation (>4.5-fold) as well as Bax to Bcl-2 protein ratio (>3.2-fold) within 2 weeks of valsartan or enalapril treatment. Immunohistological analysis revealed a significant increase in TUNEL-positive, lectin-negative non-cardiomyocytes, suggesting a rise in apoptotic interstitial fibroblasts in the left ventricle within 2 weeks of treatment with valsartan or enalapril (>63%), with a return to baseline (0.033+/-0.003%) at 4 weeks. Treatments did not affect right ventricular mass, apoptosis or cellularity.. Cardiac apoptosis induction during regression of left ventricular hypertrophy reverses interstitial fibroblast hyperplasia in SHRs treated with inhibitors of the renin-angiotensin system.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Apoptosis; Enalapril; Fibroblasts; Heart Ventricles; Hyperplasia; Hypertension; Hypertrophy, Left Ventricular; In Situ Nick-End Labeling; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazoles; Valine; Valsartan

Adenylyl cyclase (AC) messenger RNA (mRNA) expression is decreased in failing hearts. Diminished expressions are accompanied by desensitization of beta-adrenergic signal transduction. Factors contributing to such changes in mRNA expression for the major myocardial isoform AC V are not well established. To assess the contributions of hypertension, left ventricular hypertrophy (LVH), the renin-angiotensin-aldosterone system (RAS), and the sympathetic nervous system to these changes, ventricular expression of AC V mRNA was measured at different ages in spontaneously hypertensive rats (SHRs). In addition, the effects on them of angiotensin-converting enzyme inhibitor and beta-adrenoceptor antagonists were determined. Prior to quantitative Northern blotting at ages 5, 9, or 12 weeks, hemodynamic and morphologic variables were measured in SHRs and Wistar-Kyoto rats (WKYs). The SHRs and WKYs were treated with an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg/d), or a beta(1)-adrenoceptor antagonist, atenolol (100 mg/kg/d), for 8 weeks preceding Northern analysis. Myocardial AC V mRNA expression increased from 5-12 weeks in both SHRs and WKYs. Expression of AC V mRNA in SHRs increased somewhat less than in WKYs at 9 weeks and significantly less at 12 weeks. This was accompanied by development of LVH and hypertension in SHRs. Blood pressure and left ventricular weight relative to body weight were markedly decreased by enalapril and were moderately decreased by atenolol. Expression of AC V mRNA in SHRs at 12 weeks was normalized equally by enalapril and atenolol to the level of WKYs. Thus AC V mRNA expression increases are blunted in the early stages of LVH in SHRs under the influences of beta(1)-adrenergic signal transduction and the RAS.

Topics: Adenylyl Cyclases; Adrenergic beta-Antagonists; Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Atenolol; Blotting, Northern; Enalapril; Gene Expression; Heart Ventricles; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Male; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin-Angiotensin System; RNA, Messenger

The present study characterized the persistent changes (ie, off-treatment) resulting from short-term antihypertensive treatments on mean arterial pressure (MAP) and structurally based vascular resistance. Rats were treated for 14 days with enalapril (30 mg x kg(-1) x d(-1)) with regular (ENAL, 0.4%) or low salt (ELS, 0.04%) diets, or a triple therapy (Triple: hydralazine 45 mg x kg(-1) x d(-1), hydrochlorothiazide 100 mg/L, and nifedipine 200 mg/d). MAP was continuously recorded via radiotelemetry. Structurally based hindlimb vascular resistance properties (resistance at maximum dilation [Max Dil]; resistance at maximum constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn. Aortic urokinase plasminogen activator (uPA) activity was measured by zymography after 14 days of ELS. All treatments induced a significant, persistent decrease in the off-treatment MAP (ENAL downward arrow 12+/-4.6%, ELS downward arrow 16+/-2.6%, Triple downward arrow 5+/-4.17%). During treatment (14 days) the enalapril group had significant changes in the index of medial bulk (Max Con downward arrow 15+/-2.6%), but only minimal changes in lumen properties (Max Dil downward arrow 3+/-6.5%, NS). After stopping therapy, vascular properties at Max Dil were significantly decreased only in the 2 enalapril groups (ENAL downward arrow 15+/-7.9%, P<0.05; ELS downward arrow 9+/-6.0%, P<0.05; Triple downward arrow 2+/-9.8%, NS), whereas Max Con was significantly decreased in all groups (ENAL downward arrow 12+/-8.0%, ELS downward arrow 16+/-6.1%, Triple downward arrow 7+/-5.4%). At 14 days of ELS treatment, there was increased aortic uPA activity (1.6-fold). The findings reveal that various short-term antihypertensive treatments can produce persistent long-term changes in MAP and vascular structure. Further, the magnitude of the depressor response may be as important in inducing persistent changes as is the removal of angiotensin II.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Blood Vessels; Drug Therapy, Combination; Enalapril; Hindlimb; Hypertension; Hypertrophy, Left Ventricular; Kinetics; Male; Rats; Rats, Inbred SHR; Urokinase-Type Plasminogen Activator; Vascular Resistance

We report the reduction of QT and QTc dispersion in patients treated for 7 years with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. We assess the correlation between QT dispersion and LV mass during this period and at the end of an 8-week period of suspension of enalapril treatment after 5 years.. Twenty-four previously untreated patients with this condition took enalapril (20 mg twice daily) for 7 years, except during an 8-week period following 5-year follow-up. Cardiovascular parameters were determined by two-dimensional guided M-mode echocardiography, and QT interval was measured, in a pretreatment placebo phase, 8 weeks and 1, 3, 5, and 7 years after the start of the therapy, at the end of the 8-week suspension effected after 5 years, and 8 weeks after the end of the suspension.. Therapy rapidly reduced blood pressure (BP) from 156/105 mmHg to normal values: 134/84 mmHg after 8 weeks' treatment, 130-84 mmHg at 7-year follow-up (P < 0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5-year follow-up the reduction had reached 39% (P < 0.001), after which neither LV mass nor any other structural parameter underwent any further significant change. During this time, QT dispersion (DeltaQT) and the dispersion of "corrected" QT (DeltaQTc) decreased significantly: DeltaQT (from 61 +/- 21 to 37 +/- 13 ms) and DeltaQTc (from 67 +/- 27 to 41 +/- 16 ms). After suspension of treatment for 8 weeks following 5-year follow-up, DeltaQT was 40 +/- 14 ms and DeltaQTc was 44 +/- 17 ms; there were no significant changes either in DeltaQT and DeltaQTc or LV hypertrophy although BP had returned to pretreatment values (BP: 150 +/- 16; 101 +/- 10 mmHg).. Long-term enalapril treatment of hypertensive patients with LV hypertrophy induces marked regression of LV mass and improvement of QT dispersion. These improvements occur on a longer timescale than improvement in BP, and are not affected by transient changes in BP values.

Topics: Adult; Aged; Antihypertensive Agents; Comorbidity; Electrocardiography; Enalapril; Female; Heart Conduction System; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Stroke Volume; Ventricular Function, Left

To compare the effects of the sodium-hydrogen exchange blocker, amiloride, with those of the angiotensin-converting enzyme inhibitor, enalapril, on cardiac structure and function and intracardiomyocyte calcium concentration ([Ca2+]i) and pH (pHi), in spontaneously hypertensive rats (SHRs).. Experiments were performed in SHRs treated for 4 weeks with amiloride 7.5 mg/kg per day, enalapril 6.0 mg/kg per day or vehicle, and in Sprague-Dawley rats (SDRs). After haemodynamic measurements were taken, the heart was removed and weighed and hydroxyproline (a marker of collagen content) was assayed. In separate rats, ventricular myocytes were isolated, their size determined, and [Ca2+]i and pHi examined using fluo-3 acetoxymethyl ester and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein tetrakis acetoxymethyl ester fluorescence, respectively.. Left ventricular end-diastolic pressure was increased, and the maximal rates of increase and of decrease in pressure with time in the left ventricle were decreased in SHRs compared with SDRs. Myocytes were larger and hydroxyproline was increased in the left ventricle, but not in the right ventricle of SHRs compared with SDRs. Amiloride and enalapril decreased systolic blood pressure in SHRs similarly, and improved diastolic function in these rats, enalapril more than amiloride. Both agents decreased left ventricular myocyte size to similar extents; however, whereas enalapril decreased the left ventricular hydroxyproline content, amiloride did not. Left ventricular myocytes from SHRs exhibited greater [Ca2+]i and pHi than those from SDRs; enalapril decreased [Ca2+]i more than amiloride, but amiloride decreased pHi more than enalapril.. In SHRs, enalapril prevents left ventricular hypertrophy, collagen deposition, diastolic dysfunction, and increases in [Ca2+]i more effectively than does amiloride. In contrast, the latter prevents the increase in pHi more effectively than enalapril, despite similar reductions in blood pressure. These findings suggest that their effects do not depend solely on blood pressure reduction.

Topics: Amiloride; Animals; Antihypertensive Agents; Calcium; Collagen; Diuretics; Enalapril; Heart Ventricles; Hydrogen-Ion Concentration; Hypertension; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Organ Size; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Class Ib Phosphatidylinositol 3-Kinase; Cognition Disorders; Contraindications; Drug Therapy, Combination; Enalapril; Eplerenone; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Mice; Mice, Knockout; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Myocardial Reperfusion; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Receptors, Adrenergic, beta; Spironolactone

The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzothiadiazines; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Echocardiography; Electrocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Sodium Chloride Symporter Inhibitors; Time Factors

It is well established that angiotensin-converting enzyme (ACE) inhibitors (ACEI) reduce blood pressure (BP) and hypertrophy of the left ventricle and vessels. The aim of our study was to compare chemically different ACEIs regarding their ability to modulate left ventricular and media hypertrophy, ACE activity and plasma endothelin-1 concentrations in spontaneously hypertensive rats (SHRs).. After establishing equi-effective dose regimes, SHRs were treated (3 months) with captopril, enalapril, fosinopril or ramipril (2 x 25, 10, 20 or 1 mg/kg per day or corresponding 1% doses for studying blood pressure-independent effects).. Systolic blood pressure was reduced in SHRs receiving high doses of captopril, enalapril, fosinopril or ramipril (-61, -54, -35 and -47 mmHg), whereas low doses were ineffective. Left ventricular weight was decreased in animals treated with high doses (captopril/enalapril/fosinopril/ramipril: -17/-19/-17/-19%), but not low doses of agents. Media thickness of thoracal aorta was reduced by administering high doses (captopril/enalapril/fosinopril/ramipril: -31/-32/-27/-26%) and low doses (-16/-22/-22/-19%) of agents. ACE activity was reduced in heart, aorta and kidney of rats treated with high and low doses of all ACE inhibitors, whereby high doses showed more pronounced effects. Plasma endothelin-1 concentrations were not altered. A blood-pressure-ineffective treatment with an AT -antagonist revealed similar effects on cardiovascular hypertrophy.. ACEIs reduce cardiovascular hypertrophy uniformly via an AT -receptor- mediated mechanism, reinforcing the opinion that ACEI effects are indeed class effects. The significance of local renin-angiotensin systems was confirmed by antihypertrophic effects in the aorta that were apparent in the absence of any blood pressure reduction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Captopril; Circadian Rhythm; Dose-Response Relationship, Drug; Enalapril; Endothelin-1; Fosinopril; Hypertrophy, Left Ventricular; Male; Peptidyl-Dipeptidase A; Ramipril; Rats; Rats, Inbred SHR

In view of the prevalence of left ventricular hypertrophy (LVH) in patients with essential hypertension, (15-30%), with an increased risk (2-4 x) of developing myocardial infarction, heart failure or malignant arrhythmia, possibly even leading to sudden cardiac death, effective reversal of LVH is a major aim of treatment. For this purpose, angiotensin-converting enzyme (ACE) inhibitors have proved to be most suitable.. In an open bicentric study involving 37 hypertensive patients with LVH confirmed by echocardiography, the effect of spirapril in reversing the left ventricular mass index (LVMI) and diastolic left ventricular wall thickness was investigated after 3 and 6 months.. The LVMI decreased by 14.7% after 3, and by 27.3% after 6 months, irrespective of whether spirapril was given alone or in addition to other antihypertensive pre-medication. The results may be due to the proven 24-hour effect of spirapril in conjunction with the very long half-life.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Time Factors

Cardiac complications are the major cause of death in patients with beta-thalassemia major. The purpose of this study was to assess the impact of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril on left ventricular (LV) performance, with an emphasis on diastolic LV function because diastolic dysfunction has been found to be an early event in an asymptomatic thalassemic population with only mild impairment of LV systolic function.. We used echocardiography to study the impact of treatment with oral enalapril on the evolution of standard M-mode and Doppler indices, along with a recently introduced Doppler index of combined systolic and diastolic LV performance.. Patients were found to have significantly increased LV end-diastolic dimensions (LVEDD), LV end-systolic dimensions (LVESD), and left atrial dimensions and decreased LV fractional shortening (LVFS) compared with controls. After treatment with enalapril, LVESD decreased from 3.58 +/- 0.3 cm to 3.23 +/- 0.4 cm (P <.01) and LVFS increased from 32.6% +/- 4.0% to 38.0% +/- 3.1% (P <.001). Patients at baseline were found to have a significantly higher E-wave velocity, E/A ratio, and Doppler index compared with controls. The E-wave deceleration time was significantly shorter compared with that of controls. After treatment with enalapril, the E/A ratio decreased from 2.10 +/- 0.42 to 1.50 +/- 0.30 (P <.05), E-wave deceleration time increased from 0.12 +/- 0.02 seconds to 0.15 +/- 0.03 seconds (P <.01), and the Doppler index decreased from 0.46 +/- 0.10 to 0.37 +/- 0.14 (P <.05).. Enalapril was well tolerated in asymptomatic or minimally symptomatic patients with LV dysfunction resulting from beta-thalassemia major. Echocardiographically we demonstrated significant improvement in LV systolic and diastolic function. Whether this translates to improved long-term prognosis and survival remains to be further evaluated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; beta-Thalassemia; Blood Transfusion; Diastole; Echocardiography, Doppler; Enalapril; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Myocardial Contraction; Prognosis; Systole; Ventricular Function, Left

Forty male Wistar rats were separated into four groups of ten rats each (control and other three groups that have received nitric oxide (NO) synthesis inhibitor L-NAME) but the last two groups have concomitantly received antihypertensive drugs (Enalapril and Verapamil). After 40 days of experimentation, the heart and the ventricles were measured. The optical disector was used for the calculation of numerical density of the cardiomyocytes (Nv[c]). The left ventricular myocytes number (N[c]) was calculated as the product of Nv[c] and the left ventricular myocardium volume (LVMV) that was determined by using the Scherle's method. In the L-NAME group the blood pressure (BP) had a significant weekly increment. In the enalapril and the verapamil groups, BP increased in the first two weeks, but decreased in the following weeks. The LVMV increased in the L-NAME rats and decreased in the enalapril and verapamil animals. The Nv[c] and N[c] decreased in the L-NAME rats but the verapamil and enalapril treatments maintained the Nv[c] close to the control group. In conclusion, the left ventricular hypertrophy and the significant decrease of the left ventricular cardiomyocyte number caused by the NO synthesis inhibition are efficiently prevented with the use of enalapril and verapamil.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cell Count; Enalapril; Enzyme Inhibitors; Hypertrophy, Left Ventricular; Male; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Plethysmography; Rats; Rats, Wistar; Statistics, Nonparametric; Verapamil

Individually, late coronary artery reperfusion and early angiotensin converting enzyme (ACE) inhibitor therapy prevent infarct expansion post myocardial infarction (MI).. To examine the effect of late reperfusion on infarct expansion when added to early ACE inhibitor therapy post MI.. Rats were randomized into two groups: Reperfusion group: rats underwent coronary artery occlusion followed by reperfusion 2 hours after MI, a time too late to reduce infarct size. A control group: rats underwent permanent coronary artery occlusion followed by a sham operation 2 hours after MI. All rats received enalapril (2.0 +/- 0.2 mg/kg) daily in drinking water, started immediately after the second operation. Rats were sacrificed 2 weeks after coronary occlusion. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis.. Infarct size was similar in the reperfusion and control groups (23 +/- 2 vs 26 +/- 2%, p = NS). Septal thickness was also similar in both groups (1.8 +/- 0.1 vs 1.8 +/- 0.1 mm, p = NS). There was a trend towards thicker infarcts in the reperfusion group compared to the control group (0.84 +/- 0.06 vs 0.72 +/- 0.05 mm, p = 0.1). Compared to early ACE inhibition alone, late reperfusion combined with early ACE inhibition limited infarct expansion (expansion index, 1.13 +/- 0.12 vs 1.44 +/- 0.14, p < 0.05), prevented left ventricular (LV) dilation (LV volume, 0.30 +/- 0.02 vs 0.39 +/- 0.03 ml, p < 0.01) and prevented LV hypertrophy (LV weight, 0.71 +/- 0.18 vs 0.77 +/- 0.20 gm, p < 0.05).. Late coronary artery reperfusion prevents infarct expansion, LV dilation and hypertrophy even when added to early ACE inhibitor therapy post MI. This suggests that late reperfusion may be beneficial in patients with acute MI treated with early ACE inhibitor therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Combined Modality Therapy; Enalapril; Female; Heart Ventricles; Hypertrophy, Left Ventricular; Myocardial Infarction; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Tissue Fixation

Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex) and chemical stimulation (chemosensitive reflex). The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR) and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE) for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA) produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW) ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45%) as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Enalapril; Heart; Hypertension; Hypertrophy, Left Ventricular; Lung; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reflex

1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Bradykinin; Bradykinin Receptor Antagonists; Cyclosporine; Dose-Response Relationship, Drug; Drinking; Eating; Electrolytes; Enalapril; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Kallikreins; Kidney; Kidney Diseases; Male; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptor, Bradykinin B2; Renin; Sodium, Dietary; Tetrazoles; Urination; Valine; Valsartan

To test the hypothesis that the activity of enzymes degrading the extracellular matrix in hypertensive patients are abnormal, and that the treatment of hypertension will normalise these abnormalities, we measured the serum levels of metalloproteinase MMP-9, and its inhibitor, tissue metalloproteinase inhibitor (TIMP-1). Thirty-two patients with untreated hypertension (BP 168/96) had significantly lower levels of both MMP-9 and TIMP-1 when compared to 24 matched normotensive controls (BP 123/80) (P<0.001). There was no significant correlation between MMP-9 and TIMP-1 levels (P>0.2). In the patients, there were no significant correlations observed between left ventricular mass, Doppler V(E)/V(A) ratio (an index of diastolic function), blood pressure, left ventricular mass index and either MMP-9 or TIMP-1 levels (all P=NS). Levels of MMP-9 and TIMP-1 were not significantly altered after 2 months of antihypertensive treatment of 29 patients despite mean blood pressure falling from 170/96 to 143/85 mmHg (P<0.001). Correspondingly, there were also no significant alterations in indices of diastolic function and left ventricular mass. Our study suggests that the proteolytic activities of MMP-9 and TIMP-l are depressed in hypertensive patients and were not significantly affected by short-term antihypertensive treatment. The relationship between collagen metabolism in hypertensive subjects, especially in those with cardiac hypertrophy, and the effects of treatment needs to be further explored in larger trials over a longer period of time.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Collagen; Echocardiography, Doppler; Enalapril; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Matrix Metalloproteinase 9; Middle Aged; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Ventricular Function, Left

Enalopril treatment (20 mg every 12 hours) of 24 patients with essential hypertension and left ventricular (LV) hypertrophy established normal blood pressure (BP) after 8 weeks, and after 7 years had reduced LV mass index by 39% from 148 +/- 34 to 90 +/- 16 g/m2, and had normalized LV structure and function and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20, 10, and 5 mg/day during the eighth year caused no significant changes in BP, LV structure, LV systolic function, or QT dispersion, which all likewise remained unaltered during a further year of the 5-mg/day regimen. We conclude that for hypertensive patients in whom prolonged treatment with standard doses of enalapril has normalized BP, LV structure and function, and QT dispersion, significantly smaller doses are sufficient to maintain these cardiovascular achievements.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Echocardiography; Electrocardiography; Enalapril; Exercise Test; Female; Follow-Up Studies; Heart Rate; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Monitoring, Ambulatory; Physical Exertion; Systole; Ventricular Function, Left

There is some evidence that cardiac rather than circulating insulin-like growth factor-1 (IGF-1) levels contribute to the development of renovascular hypertensive left ventricular hypertrophy (LVH), remaining unknown the effects of antihypertensive drugs on IGF-1 levels. We have assessed here the preventive effects of enalapril, losartan, propanolol and alpha-methyldopa on left ventricle (LV) and circulating IGF-1 levels in a rat model of hypertension and LVH (Goldblatt, GB). Our results show that relative LV mass and the LV content of IGF-1 were significantly lower with all antihypertensive drugs in GB rats (p<0.001). Serum concentrations of IGF-1 were lower in GB rats treated with enalapril, alpha-methyldopa and propanolol (p<0.01), but not in those treated with losartan. These results support the hypothesis that local rather than seric IGF-1 contributes to the development of left ventricular hypertrophy induced by pressure overload in the rat.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Enalapril; Heart; Hypertrophy, Left Ventricular; Insulin-Like Growth Factor I; Losartan; Male; Methyldopa; Myocardium; Propranolol; Radioimmunoassay; Rats; Rats, Sprague-Dawley

Cyclosporine A (CsA)-induced hypertension has been shown to be dependent on the level of dietary salt. The present study assessed the role of the renin-angiotensin system in the development of CsA-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR) on a high-sodium diet. In addition, we examined whether ACE inhibition prevents the detrimental effects of CsA on blood pressure, kidney function and vascular morphology in SHR on high sodium intake. Eight-week-old SHR were divided into three different groups (n = 8 in each group): (i) SHR control group receiving a high-sodium diet (Na 2.6% of the dry weight of the chow), (ii) CsA group (5 mg/kg s.c.) on a high-sodium diet and (iii) CsA + enalapril group (30 mg/kg p.o.) on a high-sodium diet. At the end of the six-week experimental period, systolic blood pressure in the CsA group was significantly higher compared to the control group (245+/-6 vs 208+/-9 mmHg, respectively, p < 0.05). Plasma renin activity was increased 20-fold by CsA treatment (p < 0.05 compared to controls). CsA increased serum creatinine by 22%, the 24-h urinary protein excretion by 190% and the 24-h urinary excretions of calcium, phosphorus and magnesium by 150%, 25% and 140%, respectively (p < 0.05 compared to controls). Histologically, the kidneys of CsA-treated SHR showed severe thickening of the media of the afferent arteriole and fibrinoid necrosis of the arteriolar wall. Interestingly, CsA induced vascular injury also in the small myocardial arteries. Enalapril treatment prevented CsA-induced hypertension and deterioration of kidney function as well as CsA-induced vascular injuries in the kidneys and myocardium. Enalapril also decreased left ventricular weight-to body weight ratio and prevented CsA-induced increases in urinary calcium and phosphorus excretions. Our findings indicate that CsA has a detrimental effect on blood pressure, kidney function and vascular morphology in SHR on high sodium intake. ACE inhibition prevents the CsA-induced hypertension, nephrotoxicity and vascular injuries. Our findings thus suggest that increased activity of the renin-angiotensin system is involved in the pathogenesis of CsA-induced hypertension and nephrotoxicity in SHR on a high-sodium diet.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Creatinine; Cyclosporine; Enalapril; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Kidney; Potassium; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Sodium, Dietary

The absence of diurnal blood pressure rhythm is characteristic of patients with chronic glomerulonephritis already before they develop hypertension. The prognostic importance and possible target organ-damaging effect of the absence are unknown. Simultaneously, 24-hour ambulatory blood pressure monitoring and echocardiographic investigations were done in 12 normotensive and 38 hypertensive IgA nephropathy patients. The hypertensive patients were treated with either angiotensin-converting enzyme inhibitor (ACEI) alone or in combination with a non-dihydropyridine calcium channel blocker. The absence of a night-time blood pressure reduction was frequent in both groups (5/12 vs. 20/38). In the hypertensive patients, blood pressure and left ventricular mass index were higher (124.6 +/- 23. 3/81.2 +/- 15.3 vs. 106.6 +/- 33.4/67.4 +/- 21.8 mm Hg, p < 0.001, and 124.1 +/- 46.2 vs. 89.2 +/- 45.6 g/m(2), p < 0.01). Diastolic left ventricular function was better in normotensive patients, in whom E wave/A wave ratio (E/A) and decelaration time values correlated closely with the diastolic diurnal index (E/A, r = 0.86, p < 0.01; DT, r = -0.70, p < 0.01). In the hypertensive patients, both the left ventricular wall thickness and diastolic function were significantly related to nighttime blood pressure and diurnal index values, but there was no relationship with daytime blood pressure. In conclusion, in IgA nephropathy patients there are mild cardiac abnormalities before they develop hypertension, the abnormalities bearing the closest correlation with the decrease in diurnal blood pressure rhythm. These data suggest the inefficacy of ACEI and calcium channel blockers in treating nighttime hypertension and in reestablishing diurnal rhythm. These phenomena are of great importance in the development of left ventricular hypertrophy and diastolic malfunction.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Diltiazem; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Glomerulonephritis, IGA; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Contraction

After 7 years of treatment with 20 mg of enalapril twice daily, regression of the initial left ventricular hypertrophy in a group of 24 patients with essential arterial hypertension was achieved: gradual reduction in the dosage to 10 or 5 mg twice daily caused no worsening of either blood pressure or ventricular structure or function.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Echocardiography, Doppler, Pulsed; Enalapril; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Ventricular Function, Left

We report, in conjunction with other findings, the evolution of the dispersion of QT and QTc in patients who for the last 7 years have been treated with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. Twenty-four essential hypertensive patients who had received no previous treatment took enalapril (20 mg twice daily) for 7 years. In a pretreatment placebo phase and 8 weeks and 1, 3, 5, 6, and 7 years after the start of therapy, cardiovascular parameters were determined by two-dimensional guided M-mode echocardiography, and the QT interval and corrected QT interval (QTc) and their dispersions were obtained from amplified standard 12-lead electrocardiograms. Therapy rapidly reduced blood pressure (BP) from 156/105 mm Hg to normal values; at 7-year follow-up, BP was 130/84 mm Hg (p <0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5-year follow-up the reduction had reached 39% (p <0.001), after which neither LV mass index nor any structural parameter underwent any further significant change. LV pump function was also significantly better after 7 years of treatment. During this time, QT and QTc decreased significantly, as did the dispersion of both QT (from 61+/-21 to 37+/-14 ms) and QTc (from 67+/-27 to 41+/-16 ms). We conclude that long-term enalapril treatment of hypertensive patients with LV hypertrophy not only induces marked regression of LV mass and improved LV systolic function, but also reduces the dispersions of QT and QTc, which probably reduces the likelihood of ventricular arrhythmias and improves prognosis.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzothiadiazines; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Echocardiography; Electrocardiography; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Reproducibility of Results; Sodium Chloride Symporter Inhibitors; Stroke Volume

Quantitative 2-dimensional and Doppler echocardiography was used to assess the longitudinal effects of angiotensin-converting enzyme inhibition in asymptomatic patients with chronic, severe mitral regurgitation due to mitral valve prolapse. Over a 6-month period, angiotensin-converting enzyme inhibition therapy resulted in significant reductions in left ventricular volumes and mass in association with a minor reduction in regurgitant fraction.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Echocardiography, Doppler; Enalapril; Exercise Test; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Prolapse; Time Factors; Treatment Outcome

The prehypertrophic state of hypertensive heart disease is characterized by morphologic changes (interstitial fibrosis, increase in intramyocardial arteriolar wall thickness) as well as by functional alterations (diastolic dysfunction, decrease in coronary reserve). These changes most probably represent the earliest cardiac end-organ lesions that can clinically be detected. In cardiac hypertrophy, long-term (9-12 months) pharmacotherapy with beta-blockers, calcium channel blockers, or ACE inhibitors reverses left ventricular hypertrophy by 8% to 14%, whereas marked improvement in coronary reserve and diastolic dysfunction is achieved by calcium blocker and preferably by ACE inhibitors.

Topics: Antihypertensive Agents; Arterioles; Bisoprolol; Blood Pressure; Coronary Circulation; Diastole; Diltiazem; Disease Progression; Enalapril; Fibrosis; Heart Ventricles; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Treatment Outcome; Ventricular Dysfunction, Left

Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) is thought to produce hypertrophy in isolated cardiomyocytes via an autocrine mechanism, the pathophysiological role of HB-EGF, in myocardial hypertrophy in vivo, is not yet known. To investigate the involvement of HB-EGF in cardiac remodeling associated with hypertension in vivo, we assayed the expression of HB-EGF mRNA and protein in the left ventricle (LV) during the development of left ventricular hypertrophy in spontaneously hypertensive rats (SHR).. Prior to sacrifice and assay of HB-EGF and EGF-receptor (EGF-R) mRNA, morphologic and hemodynamic variables were measured in SHR and in age-matched Wistar Kyoto rats (WKY). At 5, 9 and 12 weeks of age, rats were killed, their hearts were removed, and the expression of HB-EGF and EGF-R mRNA and protein were measured. In addition, SHR and WKY were treated with enalapril, atenolol, or both for 4 weeks.. In untreated SHR, double products (i.e. systolic blood pressure (sBP) multiplied by heart rate (HR), an index of mechanical load, peaked at 9 weeks. Expression of HB-EGF mRNA was also observed to peak in these animals at 9 weeks, while expression of EGF-R mRNA increased from 5 to 9 weeks, but remained constant thereafter. In untreated WKY, double products and EGF-R mRNA expression did not change over time, whereas the level of HB-EGF message increased gradually. Antibody to HB-EGF reacted primarily with myocyte membranes in SHR, whereas antibody to EGF-R reacted mainly with interstitial cells in these animals. The angiotensin-converting enzyme inhibitor, enalapril, markedly decreased sBP in SHR, whereas the beta 1-adrenoreceptor antagonist, atenolol, significantly decreased HR. While neither alone affected the expression of HB-EGF mRNA, their combination significantly reduced the expression of HB-EGF mRNA, as well as double products, in these rats, but had no effect on expression of EGF-R mRNA.. The enhanced expression of HB-EGF mRNA and protein in LV of SHR suggest that this growth factor may play an important role during the early development of LV hypertrophy and cardiac fibrosis in SHR. The association between double products and HB-EGF expression suggest that the latter may be induced by increased mechanical load and may contribute, in turn, to cardiac remodeling.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antibodies; Atenolol; Biomechanical Phenomena; Drug Synergism; Enalapril; Epidermal Growth Factor; ErbB Receptors; Heparin-binding EGF-like Growth Factor; Hypertrophy, Left Ventricular; Intercellular Signaling Peptides and Proteins; Male; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model.. ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s).. Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9+/-0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis.. Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7+/-0.1 versus 2.5+/-0.4, P< 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8+/-0.1 versus 1.3+/-0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3+/-0.1 versus 2.5+/-0.4, P< 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17+/-0.01 ml versus 0.36+/-0.03 ml, P< 0.05), it remained constant in the enalapril group (0.22+/-0.02 ml versus 0.25+/-0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36+/-0.03 ml versus 0.25+/-0.03 ml, P< 0.05).. Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Female; Hypertrophy, Left Ventricular; Myocardial Infarction; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors; Ventricular Remodeling

Continued treatment of hypertensive patients with enalapril reduced left ventricular (LV) hypertrophy steadily over a period of 5 years (by which time gross structural parameters were normal) and produced no further reduction during the following 2 years. Temporary suspension of treatment after 5-year follow-up gave rise to an increase in blood pressure, and to deterioration of LV isovolumic relaxation time and deceleration of the ventricular filling E wave, both of which chiefly reflect the active relaxation of the ventricle.

Topics: Adult; Antihypertensive Agents; Echocardiography, Doppler; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Time Factors; Treatment Outcome; Ventricular Function, Left

Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.

Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Coronary Circulation; Dipyridamole; Enalapril; Heart; Hemodynamics; Hypertrophy, Left Ventricular; Imidazoles; Losartan; Male; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Vasodilator Agents

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

Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined.. IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured.. Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen.. ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Collagen; Dogs; Enalapril; Heart Ventricles; Hydroxyproline; Hypertrophy, Left Ventricular; Myocardial Infarction; Ultrasonography

Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure.. We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure.. For patients with nonischemic or ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained semiannually and evaluated in a blinded fashion. Of 99 patients in the study, aged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 +/- 23 mg/day of isosorbide dinitrate it was 153 +/- 127 mg/day.. Initial New York Heart Association classification improved from 2.8 +/- 0.9 to 1.7 +/- 0.9 (p < 0.001) in 2.7 years of follow-up. Of the 99 patients, 72 further improved their ejection fraction. For the whole group, ejection fraction increased from 21 +/- 9% to 30 +/- 13% in 6 months (p < 0.001), with a reduction in LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002), a decrease in the severity of mitral regurgitation from mild/moderate to only mild. Resting heart rate declined with no change over time in systemic systolic blood pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 +/- 16% versus 23 +/- 9% for the ischemic population.. Uptitration of high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic function, and is more effective in nonischemic than in ischemic cardiomyopathy.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Cohort Studies; Drug Therapy, Combination; Echocardiography, Doppler; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertrophy, Left Ventricular; Isosorbide Dinitrate; Male; Middle Aged; Time Factors; Vasodilator Agents; Ventricular Function, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertrophy, Left Ventricular; Multicenter Studies as Topic; Myocardial Infarction; Scandinavian and Nordic Countries; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

This study compared the effects of angiotensin converting enzyme (ACE) inhibitors captopril versus enalapril on left ventricular (LV) muscle mass and LV systolic and diastolic function in 58 patients with primary glomerulonephritis and moderate chronic renal failure. The design was a 6-8 week titration phase and 6-month maintenance phase. Mean myocardial mass calculated by M-mode echocardiography in the captopril group was 153 +/- 26 g/m2 before, and 130 +/- 14 g/m2 after 6 months of treatment, in enalapril group 147 +/- 22 g/m2 before, and 126 +/- 23 g/m2 after 6 months of treatment (p < 0.05). LV ejection fraction, early and late transmitral flow velocities and early to late LV inflow velocities ratio were not significantly affected by both ACE inhibitors.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Drug Evaluation; Enalapril; Female; Glomerulonephritis; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Remission Induction; Time Factors

Left ventricular hypertrophy (LVH) is a generalized adaptation to altered myocardial load. Hypertension induces significant increases in ventricular IGF-I gene expression that occur coordinately with development of LVH. To test whether IGF-I promotes initiation of LVH, we examined ventricular IGF-I mRNA content in spontaneously hypertensive rats (SHRs) treated with antihypertensive drugs that limit or permit LVH.. Prehypertensive SHRs were left untreated or treated with enalapril, nifedipine, or hydralazine. Systolic blood pressure (SBP), hypertrophy index (ventricular weight/body weight), and ventricular IGF-I mRNA levels were examined 2, 4, and 6 weeks after beginning therapy in the experimental groups.. Systolic blood pressure reached hypertensive levels after 2 weeks in untreated animals, and was controlled in the treated animals. The hypertrophy index in untreated animals was significantly elevated at 4 weeks. By 6 weeks, the hypertrophy indices of both the enalapril- and nifedipine-treated groups were significantly lower than that of the untreated group. In contrast, the hypertrophy index of the hydralazine-treated animals remained comparable to that of the untreated animals. By 4 weeks, IGF-I mRNA levels in the enalapril- and nifedipine-treated groups were significantly lower than those in the untreated and hydralazine-treated groups.. We conclude that: (1) antihypertensive drugs that reduce LVH blunt ventricular IGF-I mRNA content; and (2) the hemodynamic effects of antihypertensives may be dissociated from their ability to promote or limit a hypertrophic response. The clear association of LVH with ventricular IGF-I mRNA content suggests that IGF-I is an important determinant of ventricular growth. Our data also suggest that angiotensin-converting enzyme inhibitors and calcium channel blockers may reduce LVH by inhibiting cardiac IGF-I gene expression.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Enalapril; Heart; Hydralazine; Hypertension; Hypertrophy, Left Ventricular; Insulin-Like Growth Factor I; Male; Myocardium; Nifedipine; Organ Size; Rats; Rats, Inbred SHR; RNA, Messenger

There are still conflicting data as to whether reduction in LV mass is beneficial. In the present study, no deterioration in LV systolic function occurred in patients in whom regression of LV mass was achieved. Impairment in LV compliance has been shown in hypertensive patients, even in the presence of preserved systolic function and normal LV mass. In our study, improvement in diastolic function was observed only in patients whose LV mass decreased, and it was related to reduction in mass and not to a decrease in mean arterial pressure. Therefore, we suggest that because diastolic function is the first activity to deteriorate in hypertensive patients, it may be the first activity to improve, and this improvement may be related to reduction in LV mass with ACE inhibitors.

Topics: Adult; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Enalapril; Female; Fosinopril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Lisinopril; Male; Middle Aged; Ventricular Function, Left

We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Collagen; Enalapril; Heart; Heart Ventricles; Hydroxyproline; Hypertrophy, Left Ventricular; Imidazoles; Male; Pyridines; Rats; Rats, Inbred SHR

To evaluate regression of experimental left ventricular hypertrophy (LVH) in terms of its effects both on myocardial collagen levels and on diastolic stiffness.. Two-kidney, one clip Goldblatt hypertensive rats were left untreated for 4 weeks (HT4W, n = 12) or 12 weeks (HT12W, n = 11) and compared with rats the treatment of which was started after 4 weeks of hypertension with 30 mg/kg per day losartan for 8 weeks (LOS, n = 12), or 50 mg/l enalapril for 8 weeks (ENA, n = 11). A group of sham-operated rats served as controls (SHAM, n = 9).. The blood pressure of the rats increased significantly and LVH developed both after 4 and after 12 weeks of hypertension. Treatment with losartan or enalapril significantly decreased blood pressure and induced complete regression of LVH. Myocardial hydroxyproline concentrations increased in groups HT4W and HT12W (530 +/- 153 and 581 +/- 111 micrograms/g, respectively) relative to that in the SHAM group (421 +/- 22 micrograms/g). None of the treatments induced regression of increased myocardial collagen levels. The slopes of the end-diastolic stress-strain relationships in the isolated beating hearts were significantly higher in HT4W, HT12W and in both treated groups compared with those in the SHAM group, indicating increased diastolic myocardial stiffness.. Losartan and enalapril treatments decreased blood pressure and induced complete regression of LVH in this model of renovascular hypertension. In contrast, none of the treatments induced regression of increased myocardial collagen levels or reduced the abnormal left ventricular diastolic stiffness. These data suggest that diastolic dysfunction depends more on increased myocardial collagen levels than it does on myocardial mass in this model of pathological LVH.

Topics: Animals; Biphenyl Compounds; Blood Pressure; Collagen; Diastole; Enalapril; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Imidazoles; Losartan; Male; Myocardium; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Tetrazoles

To investigate the relationship between the angiotensin converting enzyme (ACE) gene polymorphism and the effects of the ACE inhibitor enalapril on left ventricular hypertrophy and impaired diastolic filling.. Enalapril (5-10 mg/day) was administered for 12 months to 60 previously untreated patients with essential hypertension. M-mode and pulsed Doppler echocardiography were performed before and after treatment, and changes in various parameters after treatment with enalapril were examined. ACE gene polymorphism was examined by the polymerase chain reaction method and the patients were classified as having the 190 bp deletion homozygous (DD) genotype, the 490 bp insertion homozygous (II) genotype or the 490 bp insertion 190 bp deletion heterozygous (ID) genotype.. The DD genotype was observed in 10 patients (17%), the ID genotype in 24 patients (40%) and the II genotype in 26 patients (43%). Plasma ACE activity before treatment with enalapril was significantly higher in seven patients with DD genotype than it was in 18 patients with ID genotype and in 14 patients with II genotype. In all of the 60 patients, the left ventricular mass index, the peak atrial systolic velocity:early diastolic velocity ratio and the deceleration time from the peak of the early diastolic wave to the baseline in transmitral flow velocity were decreased significantly after treatment with enalapril. The changes in left ventricular mass index and atrial systolic velocity:early diastolic velocity ratio after enalapril administration were significantly greater in the DD genotype group than they were in the other two genotype groups.. Enalapril-induced regression of left ventricular hypertrophy and improvement in left ventricular impaired diastolic filling were significantly greater in the DD genotype group than they were in the ID and II genotype groups, suggesting that the circulating and tissue renin-angiotensin systems, particularly the former system, are most active in hypertensive patients with the DD genotype.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Diastole; Echocardiography, Doppler, Pulsed; Enalapril; Female; Genotype; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic

The effects of enalpril (Ena, 6 mg.kg-1) and taurine (Tau, 30 mg.kg-1) on left ventricular hypertrophy (LVH) and ventricular arrhythmia were studied in two-kidney, one clip renovascular hypertensive rats (RHR). From the 9th week after operation, Ena and Tau were given per oral daily for 9 weeks. These drugs significantly decreased the systolic arterial pressure and the weight of the left ventricle. Combination of both drugs was found to reduce the blood pressure further than either drug used alone. Arrhythmias induced by trains of electrical stimuli were more frequent in working hearts isolated from RHR than that from normotensive rats. Ena and Tau could decrease the incidence of this arrhythmias in RHR. The calcium content in the myocardial mitochondria in RHR was increased compared with that in normotensive rats. Treatment with Ena and Tau reduced this increase significantly. These results suggest that chronic therapy with Ena and Tau can induce an attenuation of systemic arterial pressure and reduce the propensity of RHR heart to arrhythmogenesis by limiting cardiac hypertrophy and calcium overload of the myocardium.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Arrhythmia Agents; Blood Pressure; Calcium; Enalapril; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Male; Mitochondria, Heart; Random Allocation; Rats; Rats, Sprague-Dawley; Taurine

We investigated the potential role of increased plasma adrenomedullin and brain natriuretic peptide (BNP) levels in a patient with malignant hypertension. A 51-year-old man was admitted to our hospital with a chief complaint of visual disturbance. His blood pressure was 270/160 mmHg on admission. Papillary edema associated with retinal bleeding was observed. Echocardiography revealed marked concentric left ventricular hypertrophy with mild systolic dysfunction. Plasma levels of adrenomedullin and BNP were markedly elevated. Antihypertensive therapy reduced the plasma levels of adrenomedullin in association with a concomitant decrease in blood pressure. The plasma level of BNP also decreased and regression of left ventricular hypertrophy and normalization of left ventricular systolic function were observed. Our findings suggest that adrenomedullin may be involved in the defense mechanism against further elevations in blood pressure in patients with hypertension and that the plasma level of BNP may reflect left ventricular systolic dysfunction, left ventricular hypertrophy, or both, in patients with severe hypertension.

Topics: Adrenomedullin; Antihypertensive Agents; Atrial Fibrillation; Blood Pressure; Echocardiography; Electrocardiography; Enalapril; Humans; Hypertension, Malignant; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nicardipine; Peptides; Vision Disorders

Using M-mode and pulsed Doppler echocardiography, the effects of enalapril on left ventricular (LV) hypertrophy and diastolic dysfunction in essential hypertension and the relation between improvement in these two parameters and duration of hypertension were evaluated. The subjects, 30 previously untreated hypertensive patients, were divided into nonhypertrophy (18 patients) and hypertrophy (12 patients) groups. All patients received enalapril at a daily dose of 5 to 10 mg for 6 months. Left ventricular mass by M-mode echocardiography and LV inflow (LVIF) velocity by transthoracic pulsed Doppler echocardiography were measured before and after enalapril therapy. In the nonhypertrophy group, enalapril significantly increased peak early diastolic LVIF (E) velocity (P < .05), slightly lowered peak atrial systolic LVIF (A) velocity, significantly decreased their ratio (A/E) (P < .01), and significantly shortened both the deceleration time, from the peak of the early diastolic wave, and isovolumic relaxation time (P < .05 and P < .01, respectively). In the hypertrophy group, enalapril significantly increased E (P < .05), slightly lowered A, significantly decreased A/E (P < .05), slightly shortened the deceleration time and isovolumic relaxation time, and slightly decreased LV mass. The administration of enalapril correlated significantly and positively with the duration of hypertension and the rates of change in A/E and LV mass in all of the hypertensive patients (P < .01 and P < .05, respectively). These results suggest that long-term administration of enalapril to hypertensive patients improves LV diastolic hemodynamics regardless of the presence or absence of LV hypertrophy and that the effects are most remarkable in patients with the shortest duration of hypertension.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Flow Velocity; Enalapril; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Ultrasonography

Topics: Analysis of Variance; Animals; Drug Evaluation, Preclinical; Enalapril; Hypertrophy, Left Ventricular; Isoproterenol; Male; Rats; Statistics, Nonparametric; Time Factors

Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin-converting enzyme inhibitors (ACEI) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/kg/day), but not by enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in the losartan and captopril groups. Captopril reduced both myocardial necrosis and inflammation, whereas enalapril reduced myocardial necrosis but not inflammation. However, none of the studied losartan doses (1.2, 12, 60 mg/kg/day) influenced myocardial necrosis and inflammation resulting from viral infection. Thus, specific blockade of AII is beneficial in congestive heart failure (CHF) and LV hypertrophy but is not effective in viral-evoked inflammation and injury.

Topics: Acute Disease; Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Biphenyl Compounds; Body Weight; Captopril; Cardiovirus Infections; Enalapril; Encephalomyocarditis virus; Female; Heart; Heart Failure; Hypertrophy, Left Ventricular; Imidazoles; Injections, Intraperitoneal; Losartan; Mice; Mice, Inbred C3H; Myocarditis; Myocardium; Organ Size; Random Allocation; Tetrazoles; Therapeutic Equivalency

Clinical evaluation of hypotensive effectiveness and the cardiovascular and side effects of enalapril monotherapy of significant essential hypertension (SEH) in adolescents was performed. The studied group included 30 pts., aged from 12 to 18 years. The mean enalapril dose was 0.22 mg/kg/24 hours. Significant decrease of systolic, diastolic and mean arterial blood pressure was observed. ECHO examination performed after 6 months of therapy demonstrated significant decrease of intraventricular septum thickness, cardiac index and percentage of LV fractional shortening. Only a few minor side effects involving the GI tract were observed during therapy. We conclude that enalapril monotherapy is effective in adolescents with SEH and exerts a beneficial influence on sodium and purine balance and no adverse effect on the lipid profile. It can therefore be safely used in hypertensive patients with hyperuricemia and hypercholesterolemia. It causes regression of LV hypertrophy and improves exercise capacity.

Topics: Adolescent; Aldosterone; Child; Echocardiography; Enalapril; Evaluation Studies as Topic; Female; Gastrointestinal Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Male

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

The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinases of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin converting enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/body weight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremic state may be involved in the development of cardiac hypertrophy.

Topics: Animals; Cathepsin B; Cathepsin H; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Enalapril; Endopeptidases; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Myocardium; Rats; Rats, Wistar; Renin-Angiotensin System; Verapamil

This study compared the effects of captopril and enalapril on left ventricular geometry, function and mass and on scar collagen and topography during healing after anterior and inferior myocardial infarction in a canine model.. The beneficial effect of prolonged angiotensin-converting enzyme inhibitor therapy on remodeling during healing after myocardial infarction might be greater in anterior than inferior infarcts and more effective with captopril than enalapril therapy.. The effects of 6 weeks of therapy with captopril (50 mg twice a day), enalapril (2.5 mg twice a day) or placebo on in vivo variables of left ventricular remodeling, function and mass (by echocardiography), hemodynamic function, postmortem topography (by planimetry) and collagen (hydroxyproline levels) were studied in 36 instrumented dogs randomized to receive therapy 48 h after left anterior descending or left circumflex coronary artery occlusion.. Compared with placebo therapy, both captopril and enalapril decreased infarct expansion and thinning, progressive ventricular dilation, ventricular mass and asynergy and infarct collagen levels in anterior and inferior infarcts. Despite similar small scar sizes, the effects on remodeling and dysfunction were greater in anterior than inferior infarcts. In addition, captopril produced greater attenuation of infarct expansion and ventricular enlargement, greater improvement in volume ejection fraction and less decrease in infarct collagen levels than enalapril.. On balance, captopril and enalapril attenuated left ventricular remodeling and preserved function in small anterior and inferior infarcts despite differences in the effects of the drugs on individual remodeling variables. Further studies will be needed to determine whether inhibition of infarct collagen might be harmful, or differences between captopril and enalapril therapy important, in large transmural infarctions.

Topics: Animals; Captopril; Collagen; Dogs; Echocardiography; Electrocardiography; Enalapril; Hemodynamics; Hypertrophy, Left Ventricular; Myocardial Infarction; Systole; Time Factors; Ventricular Function, Left

Cardiac volume overload by an aortocaval shunt increases left ventricular end-diastolic pressure (LVEDP) and plasma and cardiac renin activity and results in LV hypertrophy. To a similar extent, the angiotensin-converting enzyme (ACE) inhibitors enalapril and quinapril prevent the increase in LVEDP. However, only quinapril attenuates the development of LV hypertrophy. We hypothesize that a low affinity of enalapril for cardiac ACE results in continuing generation of cardiac angiotensin II and thus hypertrophic growth of cardiomyocytes.. In the present study, we assessed plasma and cardiac angiotensins I and II 1 and 7 days after aortocaval shunt and the effects of enalapril and quinapril started 3 days before surgery on plasma and cardiac angiotensin I and II at the same time points. Aortocaval shunt increased plasma angiotensin II at 1 day by 180%, but only a small increase (by 40%) persisted at 7 days. Aortocaval shunt increased LV angiotensin II by 100% and 65% at 1 and 7 days, respectively. Both blockers similarly prevented the increase in plasma angiotensin II by aortocaval shunt at both time points. In contrast, only quinapril prevented the rise in LV angiotensin II induced by shunt at 1 and 7 days.. Aortocaval shunt increases LVEDP and plasma and cardiac angiotensin II and results in LV hypertrophy. Only prevention of the increase in LVEDP and in plasma and cardiac angiotensin II attenuates the development of LV hypertrophy, consistent with the concept that angiotensin II is involved in the development of cardiac hypertrophy by aortocaval shunt by both hemodynamic and cardiac trophic effects. This study is the first to show that differences in affinity for cardiac ACE may determine the effect of ACE inhibitors on cardiac angiotensin II and therefore cardiac hypertrophy.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Hypertrophy, Left Ventricular; Isoquinolines; Male; Myocardium; Quinapril; Rats; Rats, Wistar; Tetrahydroisoquinolines; Ventricular Pressure

Topics: Angiotensin-Converting Enzyme Inhibitors; Diastole; Echocardiography; Enalapril; Follow-Up Studies; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Ventricular Function, Left

In two-kidney-one-clip (2k-1c) renovascular hypertensive rats, the blood pressure, left ventricular weight/body weight (LVW/BW) ratio and blood platelet aggregation were increased significantly. Enalapril (Ena) 6 mg . kg-1 . d-1 ig 9 wk and Taurine 30 mg . kg-1 . d-1 ig 9 wk can not only decrease the high blood pressure, LVW/BW ratio, but also the blood platelet aggregation induced by ADP or thrombin, though still different from that of the normal group. When the 2k-1c renovascular hypertensive rats were treated with both Ena and Tau, the blood pressure and blood platelet aggregation were decreased to the same as that of the normal group, and the LVW/BW ratio was also lowered markedly, though still higher than that of the normal group. These results show that both Ena and Tau can reverse the left ventricular hypertrophy, decrease the blood pressure and suppress the blood platelet aggregation in 2k-1c renovascular hypertensive rats. When treated with both drugs, the effects can be improved. It suggests that the two drugs can enhance the effects when used together, and that they may be two good agents for treatment of hypertension.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Drug Synergism; Enalapril; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Taurine

1. New Zealand genetically hypertensive (GH) rats were treated with enalapril (20 mg/kg per day in drinking fluids) from age 4-10 weeks; one group (GHex-enal) was then taken off enalapril and followed for 6 more weeks to see if the drug-induced changes in blood pressure (BP) and structure of mesenteric resistance arteries (MRA) were long lasting once the enalapril was withdrawn. Control groups consisted of untreated GH and their normotensive (N) control strain. 2. Tail-cuff BP in GH treated rats fell significantly to N BP levels during treatment. On cessation of treatment BP rose rapidly. At age 16 weeks BP, although at a hypertensive level (mean +/- s.e.m., GHex-enal, 210.8 +/- 4.7 mmHg), was still significantly below the GH controls (230 +/- 6.9, P < 0.05), but above the N control group (137 +/- 3, P < 0.001). 3. Left ventricular (LV) mass in GH rats was reduced by enalapril to that in N rats; at the end of the subsequent period without treatment it was still significantly lower than the GH control group, but also significantly above the N group (GHex-enal, 255 +/- 6; GH 306 +/- 11; N 179 +/- 3, mg/100 g bodyweight). 4. The large changes in media, lumen and media/lumen ratio seen after 6 weeks of treatment were not sustained over the subsequent non-treatment period. However, values in the GHex-enal group at 16 weeks were closer to those in the N16 control group. 5. The persisting effects on smooth muscle (SM) cell density and SM fraction of the media contributed to an increase in SM cell volume which was significantly greater than the N16 group (P < 0.01). The number of layers of SM in the media was less than in the GH16 control group and not different from the N16 controls. 6. In GH rats the effect of ACEI on PB, LV mass and MRA structure is relatively longlasting once treatment is withdrawn.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Enalapril; Hypertension; Hypertrophy, Left Ventricular; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Rats; Vascular Resistance

The ambulatory blood pressure (BP) was recorded for 24 hours in 28 untreated hypertensive patients, and mean values of systolic (SBP) and diastolic BP (DBP) were measured over 24 hours, during the day-time (6:00 to 19:30), and during the night-time (20:00 to 5:30). M-mode echocardiography was performed and several parameters of left ventricular size were calculated. In addition, 13 men of 18 patients with left ventricular hypertrophy (LVH) received long-term treatment with enalapril, and ambulatory BP monitoring and echocardiographic measurement were performed in 10 of these patients 6 months after active treatment ended. In all 28 patients, left ventricular mass index (LVMI) was significantly related to 24-hour, day-time and night-time SBP. Other parameters of hypertrophy were correlated with 24-hour and/or night-time BP, but not with day-time BP. In patients with LVH, night-time DBP was significantly higher and the night-time decline in DBP was significantly less than in those without LVH. The 6-month treatment with enalapril clearly decreased casual and ambulatory BP and reduced LVMI. The reduction of LVMI was strongly correlated with the decrease in night-time SBP and DBP compared with the decrease in day-time BP. These observations indicate that LVH is related to 24-hour BP (especially night-time BP) and that the regression of this condition may be related to a decline in night-time BP.

Topics: Adult; Aged; Blood Pressure; Circadian Rhythm; Echocardiography; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged

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

After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure.. Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo).. The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Coronary Circulation; Enalapril; Hypertrophy, Left Ventricular; Imidazoles; Losartan; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Tetrazoles; Time Factors

To test whether angiotensin-converting enzyme (ACE) inhibition may prevent myocardial damage and may affect coronary microvasculature in spontaneously hypertensive rats (SHR), young 5-week-old SHR were treated for 3 months with spirapril and changes in blood pressure (BP) were monitored. Untreated SHR were used as controls. The rats were killed; left ventricular (LV) shape, weight, and wall thickness were examined and the ventricular myocardium was analyzed morphometrically to determine the effect of the drug on the relative amount, number per unit area of myocardium, and average dimension of foci of myocardial scarring. Moreover, volume fraction, surface, numerical density, and diffusion distance for oxygen of the coronary capillaries were analyzed. BP remained 20-30% lower in treated SHR with respect to controls, and LV weight and thickness decreased 20 and 21%, respectively. The number and dimension of the foci of fibrosis were reduced, resulting in an overall 68% decrement in the amount of myocardial damage. Finally, a 28% increment in numerical density of capillary profiles associated with a 13% reduction in their cross-sectional area decreased the diffusion distance for oxygen from the capillary wall to the myocytes by 14% in treated SHR. Spirapril decreases BP and LV weight and thickness in the SHR model of hypertension and substantially improves coronary capillary microvasculature, decreasing hypertensive myocardial damage. These results may be attributed to inhibition of the systemic effects of angiotensin II (AII) as well as to a local protective action of the drug against possible intramyocardial AII production.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Capillaries; Coronary Vessels; Enalapril; Fibrosis; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardium; Rats; Rats, Inbred SHR

The aim of this study was to study the effect of enalapril (E) on left ventricular (LV) mass, LV function and blood renin-angiotensin (RA) in patients with hypertension. Sixteen hypertensives were included in this study (WHO I 8, WHO II 8, 49.5 +/- 10.5 yrs). They were examined for blood pressure and heart rate. Chest X-ray film, echocardiography (echo), X-ray computed tomography (CT) and RA before and after about 6 months of E administration were studied. The LV mass was calculated by CT. The LV function was measured by echo. RAS was unchanged during this study. LV mass was significantly reduced after E (121.4 +/- 25.6 vs 104.6 +/- 13.7 g/cm2). The LV systolic function was unchanged after E, but LV diastolic function improved. It was shown that the long-term administration of E improves LV hypertrophy and LV diastolic function without any change of RAS.

Topics: Adult; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Renin-Angiotensin System; Tomography, X-Ray Computed; Ventricular Function, Left

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

Topics: Administration, Oral; Animals; Blood Pressure; Carnitine; Enalapril; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Myocardium; Rats; Ventricular Function, Left

To test the hypothesis that effects of angiotensin converting enzyme (ACE) inhibitors upon resistance vessel structure are responsible for their ability to cause long-term reduction in blood pressure.. Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats were treated with enalapril or hydralazine from 4 to 15 weeks of age. Effects upon tail-cuff blood pressure, left ventricular hypertrophy and structural indices of the superior mesenteric artery (SMA) and its resistance vessels were assessed at 11 weeks of treatment and up to 11 weeks post-treatment.. Left ventricular hypertrophy was assessed by left ventricular weight:body weight ratios. Evidence of vascular structural change was obtained from tissue weight:body weight ratios, levels of RNA, DNA and expression of alpha-actin and elastin messenger (m)RNA.. The effects of enalapril and hydralazine upon left ventricular hypertrophy in SHRSP were consistent with their respective effects upon blood pressure. Both drugs prevented the development of medial hypertrophy in SMA and resistance vessels. This was accompanied by substantial reductions in RNA:DNA ratios. Alpha-actin mRNA levels were not affected by either drug but elastin mRNA levels were reduced by both drugs. During the first 12 days post-treatment there was evidence of structural change in SMA accompanying the increases in blood pressure but importantly not in the resistance vessels.. The effects of enalapril upon left ventricular hypertrophy and mesenteric arterial hypertrophy are totally consistent with responses to blood pressure and the persistence of structural changes post-treatment does not underlie the ability of the ACE inhibitors to persistently suppress hypertension.

Topics: Animals; Blood Pressure; Body Weight; DNA; Elastin; Enalapril; Heart Ventricles; Hydralazine; Hypertension; Hypertrophy, Left Ventricular; Male; Mesenteric Artery, Superior; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Vascular Resistance