lisinopril and Chronic-Disease

Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics; Analgesics, Non-Narcotic; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents; Antidepressive Agents, Tricyclic; Chronic Disease; Controlled Clinical Trials as Topic; Double-Blind Method; Female; Headache; Humans; Lisinopril; Male; Meta-Analysis as Topic; Middle Aged; Migraine Disorders; Placebos; Serotonin Receptor Agonists; Sumatriptan; Tension-Type Headache; Time Factors

We report a patient who presented with malignant hypertension and renal failure. He was treated with lisinopril, spironolactone, and nifedipine retard for blood pressure control. Subsequent renal function showed further deterioration, but it then improved after withdrawal of the angiotensin converting enzyme inhibitor (ACE I). The diagnosis of classical polyarteritis nodosa was established with aneurysmal dilatation demonstrable in the renal vasculature. His renal impairment improved further following immunosuppressive therapy and the disease has remained inactive 4 years after first presentation. This is the first reported case of acute renal failure associated with the use of ACE I in polyarteritis nodosa.

Topics: Acute Kidney Injury; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Chronic Disease; Drug Therapy, Combination; Humans; Hypertension, Malignant; Lisinopril; Male; Polyarteritis Nodosa

CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.. This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.. After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.. CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Topics: Amlodipine; Antihypertensive Agents; Canada; Chlorthalidone; Chronic Disease; Coronary Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Hypolipidemic Agents; Incidence; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Proportional Hazards Models; Puerto Rico; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome; United States; United States Virgin Islands

To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose.. Multicentre crossover randomised controlled trial.. Outpatient clinics in the Netherlands.. 52 patients with non-diabetic nephropathy.. All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na(+)/day) and a regular sodium diet (target 200 mmol Na(+)/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label.. The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure.. Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na(+)/day during a low sodium diet and 184 (6) mmol Na(+)/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition.. Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Combined Modality Therapy; Cross-Over Studies; Diet, Sodium-Restricted; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Kidney Diseases; Lisinopril; Male; Middle Aged; Patient Compliance; Proteinuria; Sodium Chloride, Dietary; Tetrazoles; Treatment Outcome; Valine; Valsartan

Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers.. The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated.. The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Chemokine CCL2; Chronic Disease; Cross-Over Studies; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Imidazolidines; Inflammation Mediators; Insulin; Insulin Resistance; Interleukin-6; Japan; Lisinopril; Losartan; Male; Middle Aged; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Chronic kidney disease is common in older patients with hypertension.. To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR.. Post hoc subgroup analysis.. Multicenter randomized, double-blind, controlled trial.. Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients).. Random assignment to chlorthalidone, amlodipine, or lisinopril.. Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease).. In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure.. Proteinuria data were not available, and combination therapies were not tested.. Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

Topics: Aged; Amlodipine; Antihypertensive Agents; Cardiovascular Diseases; Chlorthalidone; Chronic Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Risk Factors

Chronic mitral regurgitation imparts a volume load on the left atrium (LA). Because this chamber may dilate asymmetrically, changes in left atrial size may be underestimated using standard two-dimensional or M-mode techniques.. The effect of lisinopril therapy in the setting of chronic organic mitral regurgitation on LA dimension was studied using standard M-mode techniques and LA volumes using the biplane Simpson's method.. Mitral regurgitant fraction was reduced at one year in the lisinopril group versus the placebo group (-6.7%+/-3.5% versus 3.5%+/-3.2%, respectively; P<0.05). Significant reductions in both maximum and minimum LA volumes were seen in the lisinopril group (88+/-33 mL to 75+/-23 mL and 46+/-20 mL to 38+/-16 mL, respectively; P<0.01). This change in LA size was not appreciated when measurements were performed using standard M-mode techniques (from 44.3+/-6.9 mm to 44.1+/-7.4 mm; P=not significant). There was no significant relationship between change in LA volume and change in regurgitant fraction or systolic blood pressure. Change in LA volume was moderately correlated with change in left ventricular mass.. Angiotensin-converting enzyme inhibitor therapy reduces LA volume in the setting of chronic mitral regurgitation. This change in LA size is not apparent when standard M-mode techniques are used. Therefore, a volumetric assessment of atrial size in the setting of chronic mitral regurgitation proved to be superior to standard two-dimensional techniques.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Volume; Chi-Square Distribution; Chronic Disease; Female; Heart Atria; Humans; Lisinopril; Male; Middle Aged; Mitral Valve Insufficiency; Observer Variation; Treatment Outcome

Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria.. In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients.. In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Hypercholesterolemia; Hypoalbuminemia; Hypotension; Kidney Diseases; Kidney Function Tests; Lisinopril; Longitudinal Studies; Male; Maximum Tolerated Dose; Middle Aged; Proteinuria; Sodium, Dietary; Treatment Outcome; Triglycerides

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Coronary Circulation; Female; Humans; Lisinopril; Male; Pulmonary Heart Disease; Treatment Outcome

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Heart Failure; Heart Ventricles; Humans; Lisinopril; Male; Middle Aged; Myocardial Infarction; Myocardium; Sclerosis; Ventricular Remodeling

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cytokines; Double-Blind Method; Endothelin-1; Female; Follow-Up Studies; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Predictive Value of Tests; Prospective Studies; Pyridines; Stroke Volume; Thiazepines; Treatment Outcome

This study was designed to fully characterize vascular tissue angiotensin I (AI)/angiotensin II (AII) conversion changes over time in vivo in humans during chronic angiotensin-converting enzyme (ACE) inhibitor therapy.. Plasma AII does not remain fully suppressed during chronic ACE inhibitor therapy. However, the plasma renin angiotensin system (RAS) might be dissociated from the vascular tissue RAS. We therefore set out to characterize the time course of vascular RAS reactivation during chronic ACE inhibitor therapy.. Vascular AI/AII conversion was studied in patients with chronic heart failure (CHF) taking chronic lisinopril therapy by the differential infusion of AI and AII into the brachial artery. A cross-sectional study was done to see whether there were differences in vascular AI/AII conversion according to New York Heart Association (NYHA) class. A second longitudinal study followed 28 patients with NYHA I to II CHF serially over 18 months to see whether vascular ACE inhibition was progressively lost with time despite ACE inhibitor therapy. A third study examined whether increasing the dose of lisinopril affected subsequent vascular ACE inhibition.. In the cross-sectional study, vascular AI-to-AII conversion was significantly reduced in NYHA class III compared with class I/II (p < 0.05). In the longitudinal study, vascular ACE inhibition was significantly reduced at 18 months as compared with baseline (p < 0.001), suggesting gradual reactivation of vascular ACE in CHF over time. In the third study, tissue ACE inhibition could be restored by increasing the ACE inhibitor dose.. Vascular AI/AII conversion reactivates over time during chronic ACE inhibitor therapy even if the CHF disease process is clinically stable. It also occurs as the CHF disease process progresses. Even if vascular AI/AII conversion has reactivated, it can be suppressed by increasing the dose of the ACE inhibitor.

Topics: Aged; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Vessels; Chronic Disease; Cross-Over Studies; Cross-Sectional Studies; Double-Blind Method; Female; Heart Failure; Humans; Lisinopril; Longitudinal Studies; Male; Middle Aged; Time Factors

To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis.. One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer.. The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found.. From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Chronic Disease; Drug Interactions; Female; Humans; Hypertension; Indomethacin; Lisinopril; Male; Middle Aged; Osteoarthritis; Tetrazoles; Treatment Outcome; Valine; Valsartan

To investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and beta-blockers would beneficially affect the measured indices.. In the cross-sectional analysis, plasma viscosity (P=0.001), fibrinogen (P=0.02), vWF (P<0.0001), and soluble P-selectin (P<0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P<0.05). Plasma viscosity (P=0.009) and fibrinogen (P=0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III-IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P=0.016) and vWF (P=0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of beta-blocker therapy, apart from a rise in mean platelet count (P<0.001).. Abnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of beta-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Arrhythmia, Sinus; Blood Platelets; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Endothelium, Vascular; Female; Fibrinogen; Heart Diseases; Hematocrit; Humans; Lisinopril; Male; Middle Aged; P-Selectin; Platelet Count; Regression Analysis; Rheology; Sex Characteristics; Solubility; Statistics, Nonparametric; Viscosity; von Willebrand Factor

The aim of the study was to determine whether Lisinopril, an ACE-inhibitor (ACEi), was more effective than other antihypertensive agents in slowing the progression of non-diabetic chronic renal diseases in patients with baseline proteinuria < or =1.0 g/day.. In an open, multicentre study all eligible patients entered a 3 months run-in phase during which antihypertensive therapy (with exclusion of ACEi) was adjusted in order to obtain a supine diastolic blood pressure < or =90 mmHg and urinary protein excretion and renal function stability were verified. One hundred and thirty-one patients with chronic renal insufficiency (Clcr between 20-50 ml/min) because of primary renoparenchymal diseases and proteinuria < or =1.0 g/day, were randomized to Lisinopril (L=66) or alternative antihypertensive therapy (C=65). Changes in renal function were assessed by inulin (Clin) clearance.. During the follow-up period of 22.5+/-5.6 months, Clin did not change significantly in group L (-1.31+/-0.6 ml/min/1.73 m(2)) differing significantly from group C in which it declined markedly (-6.71+/-3.6 ml/min/1.73 m(2)) (P<0.04). Seven patients experienced adverse events that prompted discontinuation of treatment: four in group L and three in group C; in addition seven patients showed severe deterioration in renal function requiring dialysis: two in group L and five in group C. The overall risk of the combined end-points: need for dialysis or halving of GFR was significantly higher in group C versus group L. During the study the mean value for systolic blood pressure was 137.8+/-14.6 SD mmHg in group L and 140.8+/-14.1 SD mmHg in group C; the mean difference between groups, during and at the end of the study, was 2 mmHg (NS). The mean diastolic blood pressure during the study was 83.8+/-8.6 SD mmHg in group L and 84.3+/-7.56 SD mmHg in group C; during and at the end of the study the mean diastolic difference between groups was 1 mmHG:. This study, employing a sensitive measurement of renal function and with similar blood pressure in both groups, provides support to the hypothesis that ACEi have a specific renoprotective effect, in addition to blood pressure control, also in patients with mild proteinuria.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Blood Pressure; Chronic Disease; Diastole; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Prospective Studies; Protective Agents; Proteinuria

Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38+/-12 years; mean+/-S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measurement of forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasodilators and an endothelial-dependent vasoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-L-arginine (L-NMMA) respectively] using venous occlusion plethysmography. Lisinopril significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12+/-0.37 (mean+/-S.E.M.); placebo, 2.58+/-0.25; P=0.02, 95% confidence intervals (CI) 0.09, 1.06] (values given are ratios of flow in the infused arm to that in the control arm); there was no effect on the response to sodium nitroprusside (lisinopril, 3.97+/-0.40; placebo, 3.92+/-0.39; P=0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to L-NMMA demonstrated a significant improvement (lisinopril, 0.77+/-0.06; placebo, 0.95+/-0.05; P<0.001; 95% CI -0.09, -0.27). In conclusion, these results indicate that ACE inhibition can improve endothelial function in cigarette smokers. We show that lisinopril improves both receptor-mediated and tonic NO release. The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release.

Topics: Acetylcholine; Adult; Angiotensin-Converting Enzyme Inhibitors; Arm; Chronic Disease; Confidence Intervals; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Humans; Linear Models; Lisinopril; Male; Nitric Oxide; Nitroprusside; omega-N-Methylarginine; Plethysmography; Regional Blood Flow; Smoking; Vasoconstrictor Agents; Vasodilator Agents

An analysis was designed to determine whether chronic heart failure patients at high cardiovascular risk benefited to the same extent from high-dose lisinopril as the whole ATLAS population.. A retrospective analysis was performed on high-risk heart failure patients in the Assessment of Treatment with Lisinopril And Survival (ATLAS) trial (total number of patients 3164) comparing highdose (32.5-35 mg. day(-1)) vs low-dose (2.5-5 mg. day(-1)) lisinopril for a median of 46 months. These high-risk patients included those with hypotension, hyponatraemia, compromised renal function, the elderly and patients with diabetes mellitus at baseline. In the whole study population, high-dose lisinopril led to a trend in risk reduction of all-cause mortality (primary end-point P=0.128) and a significant risk reduction in all-cause mortality plus hospitalization (principal secondary end-point P=0.002). Subgroup analyses were performed for these end-points. There were no consistent interactions between age, baseline sodium, creatinine or potassium values, and treatment effect. Diabetics showed a beneficial response to high-dose therapy that was at least as good as that in non-diabetics. The underlying higher morbidity/mortality rates in diabetics mean that high-dose lisinopril has potential for a larger absolute clinical impact in these patients.. Long-term high-dose lisinopril was as effective and well-tolerated in high-risk patients, including those with diabetes mellitus, as for the ATLAS study population as a whole.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Databases, Factual; Diabetes Complications; Drug Administration Schedule; Female; Heart Failure; Hospitalization; Humans; Lisinopril; Male; Middle Aged; New York; Randomized Controlled Trials as Topic; Retrospective Studies; Survival Analysis

This study was designed to compare different proposed methods of assessing adherence with angiotensin-converting enzyme (ACE) inhibitor (ACEI) therapy in chronic heart failure.. The use of ACEIs in chronic heart failure gives us a unique opportunity to assess a patient's adherence by measuring whether the expected biochemical effect of an ACEI is present in the patient's bloodstream. In fact, there are several different ways of assessing ACE in vivo: these are serum ACE activity itself, plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), urine AcSDKP, plasma angiotensin I (AI), plasma angiotensin II (AII), or the AII/AI ratio.. Patients with chronic heart failure (n = 39) were randomized to regimens of ACEI nonadherence for one week, ACEI adherence for one week or two versions of partial adherence for one week, after which the above six tests were performed.. All six tests significantly distinguished between full nonadherence for one week and full or partial adherence. Only plasma AcSDKP produced a significantly different result between partial adherence and either full adherence or full nonadherence for one week. In terms of their ability to distinguish full nonadherence from full adherence, plasma AcSDKP was 89% sensitive and 100% specific with an area under its ROC of 0.95. Corresponding figures for urine AcSDKP were 92%, 97% and 0.95 and for serum ACE they were 86%, 95% and 0.90.. All six tests distinguished full nonadherence from all other forms of adherence. The rank order of performance was plasma AcSDKP, urine AcSDKP, serum ACE, AII/AI ratio and plasma AII followed by plasma AI.

Topics: Aged; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chronic Disease; Diuretics; Drug Therapy, Combination; Echocardiography; Furosemide; Heart Failure; Humans; Lisinopril; Oligopeptides; Peptidyl-Dipeptidase A; Radionuclide Ventriculography; Treatment Outcome; Treatment Refusal

This study was designed to determine regional differences in patient characteristics and medication use among patients entered into an international heart failure trial.. Data for this analysis were derived from the Assessment of Treatment with Lisinopril and Survival Study (ATLAS), a prospective randomized comparison of high- and low-dose therapy with lisinopril in patients with New York Heart Association class II, III, or IV chronic heart failure, which enrolled 3164 patients in 291 centers in 19 countries on 3 continents. Information was collected at baseline concerning patient demographics, etiology of heart failure, accompanying conditions, prior revascularization procedures, and medication use. The primary findings were a lower incidence of ischemic cardiomyopathy in southern and western Europe, more frequent diabetes in North America, and a greater use of coronary revascularization in the United States and Canada. There was substantial variation in medication use, particularly with regard to digoxin, anticoagulants, and amiodarone.. Although there is considerable overlap in guidelines concerning the treatment of heart failure issued by authorities in Europe and North America, there are significant regional variations in medication use. Some, but not all, of these differences can be explained by differences in patient characteristics.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Canada; Chronic Disease; Dose-Response Relationship, Drug; Europe; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; North America; Patient Selection; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; United States

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Chronic Disease; Combined Modality Therapy; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Lisinopril; Male; Middle Aged; Remission Induction; Renal Dialysis; Time Factors; Uremia

Although atrial fibrillation is common in patients with heart failure, patients with atrial fibrillation are often excluded from congestive heart failure trials or are not analyzed separately. Consequently, while the effect of angiotensin-converting enzyme inhibitors in patients with sinus rhythm is well established, the effect on patients with atrial fibrillation is unknown. The authors hypothesized that these agents might be particularly effective in this patient category, given their antiadrenergic properties and the importance of adequate rate control. Therefore, the effects of lisinopril 10 mg once daily were evaluated in 30 patients with congestive heart failure and chronic atrial fibrillation (mean age, 68 +/- 6 years) in a double-blind, randomized, placebo-controlled trial. All patients were in New York Heart Association class II or III and were stable on conventional therapy (digoxin, diuretics, nitrates). After 6 weeks, mean peak oxygen consumption increased from 14.7 +/- 3.4 to 15.9 +/- 2.9 mL/min/kg in the lisinopril group (P = .034). Plasma norepinephrine levels during exercise and at peak exercise tended to be lower when the patients were taking lisinopril (10.8 +/- 4.2 to 8.9 +/- 4.4 nmol/L and 16.3 +/- 9.2 to 14.3 +/- 7.7 nmol/L, P < .1). Heart rate during exercise and ambulatory monitoring was not significantly affected. Left ventricular fractional shortening tended to increase after lisinopril (23 +/- 7 to 27 +/- 9%, P = .073). Left atrial volume was unchanged, as were plasma atrial natriuretic peptide levels. After subsequent electrical cardioversion, treatment was continued for 6 more weeks, allowing assessment of the effect of lisinopril on maintenance of sinus rhythm; maintenance of sinus rhythm was 71% in the lisinopril group and 36% in the placebo group (P = NS). This study shows that treatment with an angiotensin- converting enzyme inhibitor improves peak oxygen consumption in patients with congestive heart failure and chronic atrial fibrillation. Attenuation of adrenergic drive during exercise may play a role in mediating this effect.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Electric Countershock; Exercise Test; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prospective Studies; Ventricular Function, Left; Ventricular Premature Complexes

The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.

Topics: Adult; Aged; Captopril; Chronic Disease; Double-Blind Method; Female; Glomerulonephritis; Humans; Lisinopril; Male; Middle Aged; Proteinuria

The acute hypotensive response to oral and parenteral enalapril (E) and lisinopril (LI) was assessed in 24 patients with chronic congestive heart failure in two open, randomized, balanced, crossover studies. In the E study, 12 patients received each of three treatments: a single oral dose of 10 mg E, a single intravenous bolus of 5 mg E, and a single intravenous bolus of 5 mg enalaprilat (ET). In the LI study, 12 patients received each of two treatments: a single oral dose of 10 mg LI and a single intravenous bolus of 5 mg LI. Intraarterial blood pressure was measured continuously. Significant decreases from baseline in mean arterial pressure (MAP) were observed in all cases, starting at 15 min. The maximal hypotensive effect (MAP; mean +/- SD) was greatest and the nadir earliest for intravenous ET (-30 +/- 7 mm Hg at 75 min) compared with oral E (-25 +/- 10 mm Hg at 210 min) and intravenous E (-19 +/- 10 mm Hg at 195 min). Oral E and intravenous E had similar onsets of action. The maximal reduction following oral LI (-19 +/- 13 mm Hg at 210 min) was similar to oral E and intravenous E. The effect of intravenous LI (-25 +/- 9 mm Hg at 105 min) was similar to that of intravenous ET. Among the parenteral treatments, E produced the most gradual and least pronounced reduction in blood pressure, and may be best suited for use in the acute situation to minimize the risk of abrupt hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Blood Pressure; Chronic Disease; Enalapril; Enalaprilat; Female; Heart Failure; Humans; Hypotension; Injections, Intravenous; Lisinopril; Male; Middle Aged

Peripheral angioedema of the face and upper airways is a well-known phenomenon of angiotensin-converting enzyme inhibitors occurring in only 0.1% to 0.7% of patients. We describe a case of the even less-common manifestation of visceral angioedema, which causes symptoms of chronic and intractable diarrhea.. A 68-year-old white woman presented with large-volume diarrhea, caused by visceral angioedema secondary to lisinopril therapy. Initial imaging studies were significant for distended small bowel loops, with subsequent unremarkable findings on colonoscopy and biopsy studies. After an exhaustive laboratory work-up, her diarrhea resolved only after the discontinuation of lisinopril.. Use of angiotensin-converting enzyme inhibitors is increasing, making the recognition of visceral angioedema important in preventing significant morbidity and avoiding invasive and costly studies.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Diarrhea; Female; Humans; Lisinopril

The somatic isozyme of ACE (angiotensin I-converting enzyme) comprises two distinct zinc-dependent catalytic domains with different substrate specificities for angiotensin I (cleaved selectively by the C-domain) and bradykinin (cleaved equally efficiently by both the N- and C-domains). Classical ACEIs (ACE inhibitors) target both domains, with side effects such as cough and angio-oedema being attributed, in part, to N-domain inhibition, probably through bradykinin accumulation. We questioned whether a novel C-domain-selective ACEI (lisW-S) has anti-hypertensive effects without influencing bradykinin status. AngII (angiotensin II)-dependent hypertension was studied in mice that express active human renin in the liver (TtRhRen). Compared with wild-type littermates, TtRhRen mice displayed cardiac hypertrophy and had significantly elevated SBP [systolic BP (blood pressure)] as determined by tail cuff sphygmomanometry (150±3 compared with 112±5 mmHg; P<0.05) and telemetry (163±3 compared with 112±2 mmHg; P<0.01). Treatment with the non-selective ACEI lisinopril (1 mg/kg of body weight per day via an osmotic mini-pump for 2 weeks) reduced SBP (127±3 compared with. 154±6; P<0.05). Similarly, treatment with the C-domain selective ACEI lisW-S (lisinopril-tryptophan; 3.6 mg/kg of body weight per day via an osmotic mini-pump for 2 weeks) reduced BP. Treatment with lisinopril or lisW-S significantly reduced levels of AngII in kidneys (~4-fold; P<0.001). Ang-(2-8) [angiotensin-2-8)] was significantly reduced by lisinopril, but not by lisW-S. Plasma bradykinin levels were significantly increased only in the lisinopril group. These data suggest that C-domain-selective ACEIs reduce BP and AngII levels similarly to classical ACEIs. C-domain-selective ACEIs have the potential to avoid undesirable effects on the bradykinin system common to classic ACEIs and may represent a novel approach to the treatment of hypertension.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Bradykinin; Cardiomegaly; Chronic Disease; Disease Models, Animal; Drug Evaluation, Preclinical; Hypertension; Hypertrophy; Kidney; Lisinopril; Mice; Mice, Transgenic

Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure.. To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens.. According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg.. 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes.. In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Creatinine; Diabetes Mellitus; Diuretics; Drug Therapy, Combination; Enalapril; Epidemiologic Methods; Female; Heart Failure; Humans; Lisinopril; Male; Reference Values; Renal Insufficiency; Risk Factors

Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia.. We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m(2)) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score.. We followed 5171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors.. The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperkalemia; Kidney Diseases; Lisinopril; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk; Risk Factors

Cardiac hypertrophy in a patient with severe iron deficiency anaemia associated with long-term bloodletting using cupping, called 'puhang' in oriental medicine, is discussed using chest electrocardiographic and radiographic images. With iron supply, the patient showed remarkable improvement of cardiomegaly, which is a unique feature of chronic severe iron deficiency anaemia.

Topics: Aged; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Cardiomegaly; Chronic Disease; Diuretics; Female; Furosemide; Heart Failure; Humans; Iron Compounds; Lisinopril; Phlebotomy; Treatment Outcome; Ultrasonography

Topics: Aged; Amlodipine; Antihypertensive Agents; Cardiovascular Diseases; Chlorthalidone; Chronic Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Risk Factors

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.

Topics: Actins; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Body Weight; Chronic Disease; Cytokines; Dose-Response Relationship, Drug; Drug Synergism; Fibrosis; Genes, ras; Hydroxyproline; Immunohistochemistry; Lisinopril; Male; Organ Size; Pancreatitis; Peptidyl-Dipeptidase A; Peroxidase; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; RNA, Messenger; Tetrazoles

Neovascularization in the retina and iris of diabetic patients is a major cause of severe visual loss. However, study of these lesions is compromised by the lack of a comparable diabetic rodent model. Because the vasoactive and angiogenic agent, angiotensin II, is involved in diabetic microvascular disease, we aimed to determine whether endothelial cell proliferation could be induced in the retinae and irides of hypertensive transgenic (mRen-2)27 rats that display an enhanced extra-renal renin-angiotensin system (RAS), including the eye. Six-week-old Ren-2, spontaneously hypertensive, and Sprague-Dawley rats received either streptozotocin or control vehicle and were studied for 36 weeks. Additional nondiabetic and diabetic Ren-2 rats were treated throughout with the angiotensin-converting enzyme inhibitor lisinopril (LIS) (10 mg/kg/day in drinking water). Endothelial cell proliferation was only observed in retinae and irides of diabetic Ren-2 rats and was reduced with LIS. In diabetic Ren-2, vascular endothelial growth factor (VEGF) and VEGFR-2 mRNA were increased in retinae and irides and reduced with LIS. Diabetes activated ocular renin in Ren-2 but not Sprague-Dawley rats. The diabetic Ren-2 rat is a model of intraocular endothelial cell proliferation that can be attenuated by RAS blockade via VEGF-dependent pathways. RAS blockade is a potential treatment for vision-threatening diabetic microvascular complications.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Genetically Modified; Chronic Disease; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Disease Models, Animal; Endothelial Growth Factors; Endothelium, Vascular; Eye; Female; Heterozygote; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Iris; Lisinopril; Lymphokines; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Renin; Renin-Angiotensin System; Retina; RNA, Messenger; Streptozocin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors

To determine if B-type natriuretic peptide (BNP) measurement could be useful in determination of functional capacity in patients suffering from chronic heart failure.. Evaluating functional capacity is a crucial factor in the follow-up of patients with chronic heart failure. There are numerous methods for measuring functional capacity and their relative merits remain under discussion. Clinical classifications are very subjective and other methods are difficult to use in clinical practice.. We evaluated functional capacity in 151 consecutive patients using the 6-min walk test. All patients were clinically classified using the New York Heart Association (NYHA) classification. We measured BNP plasma levels using a bedside BNP test.. Six minute walk test performance decreased through NYHA classes 1 to 4 (469+/-87, 411+/-82, 325+/-83 and 196+/-63 m, respectively, P<0.01) and BNP levels increased through NYHA classes 1 to 4 (26.3+/-7.2, 73+/-13, 401+/-74 and 924+/-84 pg/ml, respectively, P<0.001). There was a significant correlation between 6-min walk test performance and BNP plasma levels (R=0.69 P<0.001) and a weaker correlation between BNP and left ventricular ejection fraction (R=0.45 P<0.04). In some patients there was a mismatch between NYHA classification and 6-min walk test performance. In all cases BNP could correct the clinical estimation of functional capacity. When we divided the patients into three sub-groups within each NYHA class, we showed that using BNP could better define functional capacity in patients suffering from chronic heart failure in NYHA classes I to III.. The measurement of BNP levels thus usefully supplements the clinical examination. The existence of bedside BNP testing methods facilitates its use in routine clinical practice. It also permits easier follow-up of patients with chronic heart failure.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Follow-Up Studies; France; Furosemide; Heart Failure; Humans; Incidence; Lisinopril; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Severity of Illness Index; Spironolactone; Stroke Volume; Treatment Outcome

Pancreatic stellate cells have some similarities to hepatic stellate cells and an intrinsic renin-angiotensin system is present in the pancreas and is enhanced in acute pancreatitis and chronic pancreatic hypoxia. We assessed the effects of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, on spontaneously occurring chronic pancreatitis.. Lisinopril in drinking water (20, 50, or 200 mg/L) was administered to 10-week-old male Wistar Bonn/Kobori (WBN/Kob) rats for 10 weeks and then the inflammatory parameters, fibrosis, serum and pancreatic ACE activity, and expression of transforming growth factor-beta1 (TGF-beta1) messenger RNA (mRNA) as well as positive immunostaining for alpha-smooth muscle actin (alpha-SMA) were assessed.. Lisinopril attenuated gross alterations in the pancreas. This protective effect was confirmed quantitatively by significant increases in pancreatic weights and decreases in pancreatic myeloperoxidase (MPO) activity (an index of granulocyte infiltration), pancreatic hydroxyproline content (an index of collagen deposition), ratio of fibrous tissue, and histologic scores. Lisinopril significantly reduced serum ACE activity but it did not affect pancreatic activity. High doses of lisinopril suppressed the overexpression of TGF-beta1 mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and decreased the number of alpha-SMA-positive cells (activated pancreatic stellate cells) in the pancreas.. Lisinopril alleviated chronic pancreatitis and fibrosis in male WBN/Kob rats. It suppressed the expression of TGF-beta1 mRNA, resulting in the prevention of pancreatic stellate cell activation, which may be involved in the observed protection. We propose that an ACE inhibitor may be useful for treating chronic pancreatitis.

Topics: Actins; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Chronic Disease; Fibrosis; Gene Expression; Hydroxyproline; Immunohistochemistry; Lisinopril; Male; Organ Size; Pancreas; Pancreatitis; Peptidyl-Dipeptidase A; Peroxidase; Rats; Rats, Wistar; Transforming Growth Factor beta; Transforming Growth Factor beta1

By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF).. Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs.. Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136).. This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.

Topics: Adult; Aged; Aged, 80 and over; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Arteries; Aspirin; Blood Pressure; Chronic Disease; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Diastole; Dose-Response Relationship, Drug; Enalapril; Endpoint Determination; Female; Heart Failure; Heart Rate; Humans; Lisinopril; Male; Manometry; Middle Aged; Observer Variation; Prospective Studies; Ramipril; Renin; Reproducibility of Results; Single-Blind Method; Systole; Thromboxane B2; Time Factors; Treatment Outcome

(1) Increased vascular resistance in chronic heart failure (CHF) has been attributed to stimulated neurohumoral systems. However, local mechanisms may also importantly contribute to set arterial tone. Our aim, therefore, was to test whether pressure-induced myogenic constriction of resistance arteries in vitro--devoid of acute effects of circulating factors--is increased in CHF and to explore underlying mechanisms. (2) At 12 weeks after coronary ligation-induced myocardial infarction or SHAM-operations in rats, we studied isolated mesenteric arteries for myogenic constriction, determined as the active constriction (% of passive diameter) in response to stepwise increase in intraluminal pressure (20 - 160 mmHg), in the absence and presence of inhibitors of potentially involved modulators of myogenic constriction. (3) We found that myogenic constriction in mesenteric arteries from CHF rats was markedly increased compared to SHAM over the whole pressure range, the difference being most pronounced at 60 mmHg (24+/-2 versus 4+/-3%, respectively, P<0.001). (4) Both removal of the endothelium as well as inhibition of NO production (L-N(G)-monomethylarginine, 100 micro M) significantly increased myogenic constriction (+16 and +25%, respectively), the increase being similar in CHF- and SHAM-arteries (P=NS). Neither endothelin type A (ET(A))-receptor blockade (BQ123, 1 micro M) nor inhibition of perivascular (sympathetic) nerve conduction (tetrodotoxin, 100 nM) affected the myogenic response in either group. (5) Interestingly, increased myogenic constriction in CHF was fully reversed after angiotensin II type I (AT(1))-receptor blockade (candesartan, 100 nM; losartan, 10 micro M), which was without effect in SHAM. In contrast, neither angiotensin-converting enzyme (ACE) inhibition (lisinopril, 1 micro M; captopril, 10 micro M) or AT(2)-receptor blockade (PD123319, 1 micro M), nor inhibition of superoxide production (superoxide dismutase, 50 U ml(-1)), TXA(2)-receptor blockade (SQ29,548, 1 micro M) or inhibition of cyclooxygenase-derived prostaglandins (indomethacin, 10 micro M) affected myogenic constriction. (6) Sensitivity of mesenteric arteries to angiotensin II (10 nM - 100 micro M) was increased (P<0.05) in CHF (pD(2) 7.1+/-0.4) compared to SHAM (pD(2) 6.2+/-0.3), while the sensitivity to KCl and phenylephrine was not different. (7) Our results demonstrate increased myogenic constriction in small mesenteric arteries of rats with CHF, potentially making it an i

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Biphenyl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Captopril; Chronic Disease; Coronary Vessels; Disease Models, Animal; Endothelium-Dependent Relaxing Factors; Endothelium, Vascular; Fatty Acids, Unsaturated; Heart; Heart Failure; Hydrazines; Imidazoles; Indomethacin; Lisinopril; Losartan; Male; Mesenteric Arteries; Nitric Oxide; omega-N-Methylarginine; Pyridines; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Superoxide Dismutase; Sympathetic Nervous System; Tetrazoles; Tetrodotoxin; Vascular Resistance

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Drug Administration Schedule; Heart Failure; Humans; Lisinopril; Randomized Controlled Trials as Topic

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Cough; Humans; Lisinopril; Male

In several models of renal disease progression, angiotensin-converting enzyme (ACE) inhibitors reduced proteinuria and limited glomerulosclerosis, which suggested that reduction of renal angiotensin II (Ang II) activity is crucial for the preservation of glomerular structure and function. However, it cannot be ruled out that other hormonal systems, including inhibition of the bradykinin breakdown, also play a role. We compared the effects of chronic treatment with the ACE inhibitor lisinopril with those of a specific Ang II receptor antagonist, L-158,809, on proteinuria and renal injury in passive Heymann nephritis (PHN), a model of immune renal disease that closely resembles human membranous nephropathy, with long-lasting proteinuria followed by tubulointerstitial damage and glomerulosclerosis. Passive Heymann nephritis was induced with 0.5 mL/100 g of rabbit anti-Fx1A antibody in 24 male Sprague-Dawley rats. The animals were divided into three groups of eight rats each, and were given the following in the drinking water on a daily basis: lisinopril (40 mg/L), L-158,809 (50 mg/L), or no therapy. Treatment started at day 7 (proteinuria was already present) and lasted 12 months. Eight normal rats were used as controls. Untreated PHN rats developed hypertension, while rats with PHN given lisinopril or L-158,809 all had systolic blood pressure values even lower than those of normal rats. Urinary protein excretion progressively increased with time in untreated PHN rats, who developed tubulointerstitial damage and glomerulosclerosis. Both lisinopril and L-158,809 exhibited a potent antiproteinuric effect and preserved glomerular and tubular structural integrity at a similar extent. Renal gene expression of transforming growth factor-beta and extracellular matrix proteins was also effectively reduced by the two treatments. These results indicate that ACE inhibitors and Ang II receptor antagonists are equally effective in preventing renal injury in PHN and suggest that the renoprotective effects of ACE inhibitors in this model are solely due to inhibition of Ang II.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Chronic Disease; Extracellular Matrix Proteins; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Imidazoles; Kidney; Lisinopril; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Renal Plasma Flow; Tetrazoles; Transforming Growth Factor beta

The increased sympathetic drive in chronic heart failure (CHF) might provoke vascular adrenoceptor desensitization, which, together with endothelial dysfunction, could contribute to the altered vasomotor tone seen in CHF. We investigated 1) whether CHF alters the responses mediated by alpha and beta adrenoceptors in small and large peripheral arteries, and 2) the effect of angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d) starting 7 days after ligation. Responses to phenylephrine (alpha 1 agonist), salbutamol (beta 2 agonist) as well as acetylcholine (endothelium-dependent), were assessed after 3 months in isolated and pressurized segments of the abdominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arteries, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the responses to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional area and collagen density. Thus, the unchanged arterial responsiveness to adrenoceptor agonists does not indicate any vascular adrenoceptor desensitization, while endothelial dependent vasodilation of small arteries is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the effect ACE inhibitors have on exercise tolerance and survival.

Topics: Acetylcholine; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Albuterol; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Abdominal; Chronic Disease; Endothelium, Vascular; Femoral Artery; Heart Failure; Hemodynamics; In Vitro Techniques; Lisinopril; Male; Mesenteric Arteries; Muscle Contraction; Muscle Relaxation; Neurotransmitter Agents; Nitroprusside; Phenylephrine; Rats; Rats, Wistar; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Renin-Angiotensin System

ACE inhibitors are used world-wide for treatment of hypertension and cardiac failure; liver damage is a rare but potentially severe side-effect of these drugs. In this case report we describe a patient with chronic liver damage due to lisinopril.

Topics: Chemical and Drug Induced Liver Injury; Chronic Disease; Humans; Hypertension; Lisinopril; Male; Middle Aged

Topics: Amlodipine; Animals; Blood Pressure; Cardiomegaly; Chronic Disease; Lisinopril; Male; Muscle Proteins; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY

1. In addition to their antihypertensive effect, ACE inhibitors have been reported to increase general well-being, general health and vitality and work performance. The cause of these effects is not known. A possible mechanism may be release of beta-endorphins. 2. In the present study changes in plasma concentration of beta-endorphins on days with ACE inhibitor treatment (n = 12) and on non-treatment control days (n = 12) were compared in 6 patients. 3. Both on control and treatment days the beta-endorphin level fell, by 7.1 and 10.0%, respectively, from 8.00 a.m. to 8.00 p.m., reflecting the known diurnal rhythm of this opioid. This difference between the control and treatment days is not statistically significant. 4. The study should be extended to determine endorphin concentration in the cerebrospinal fluid, and other opioids should be looked for.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Endorphins; Female; Heart Failure; Hemodynamics; Humans; Lisinopril; Male

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Drug Evaluation; Enalapril; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Lisinopril; Middle Aged; Potassium; Proteinuria; Renin