PATHOGENETIC ADVANCES OF FOSINOPRIL SODIUM WITH HYDROCHLOROTHIAZIDE IN OBESE HYPERTENSIVE PATIENTS.

Purpose - to improve antihypertensive therapy on the basis of studying the antioxidant properties of an angiotensin-converting enzyme (ACE) inhibitor (fosinopril sodium) and a diuretic (hydrochlorothiazide), their impact on endothelial dysfunction and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of fosinopril sodium 20 mg/day and hydrochlorothiazid 12.5 mg/day was prescribed to 54 patients with essential hypertension of 1-3 grades, 30 to 65 years old . The control group included 10 healthy subjects matched for age and sex. During the course of combined antihypertensive therapy we observed a significant decrease of i-NOS activity, reduce of TNF-α type I of its soluble receptor (sTNF-αRI), and 8-iso-PgF2α in the patients. Activity of e-NOS, superoxide dismutase and catalase, in contrast, were increased in patients with hypertension and concomitant obesity. Thus, the improvement of endothelial function, a significant decrease autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of fosinopril sodium and hydrochlorothiazid for differentiated therapy in hypertensive patients with obesity.

Angiotensin Converting Enzyme Inhibitor Dialyzability and Outcomes in Older Patients Receiving Hemodialysis.

BACKGROUND/AIMS: Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis ('high dialyzability'), whereas others are not ('low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors. METHODS: Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all-cause mortality within 180 days of first ACE inhibitor prescription. RESULTS: There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9-1.3, p = 0.6). CONCLUSION: In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes.

[The use of complex tools ezetimibe, hepadyfu fosinopril and correction of blood pressure and endothelial dysfunction in patients with nonalcoholic steatohepatitis and essential hypertension stage II].

The article investigates the impact of complex tools fosinopril, hepadyf and ezetimibe for correction of functional state of the endothelium and changes in blood pressure in patients with nonalcoholic steatohepatitis, obesity and essential hypertension stage II.

[CLINICAL PERSPECTIVES OF COMPLEX APPLICATION OF PERCUTANEOUS CORONARY INTERVENTION AND DRUG REVASCULARIZATION IN ACUTE CORONARY SYNDROME].

The article presents the evaluation of the influence of complex application of monopril, propranolol and heparin and percutaneous coronary intervention (PCI); monopril, propranolol with methylase in combination with PCI and PCI only on hemddynamics, cardiohemodynamics and clinical course in acute myocardial infarction (MI), as well as the monitoring of these patients. A comparison of the results of the complex medical and mechanical revascularization. The study involved 63 patients with acute coronary syndrome (ACS): anterior MI with Q wave and ST-segment with the rise in age from 30 to 70 years, the average age (56.7 +/- 1.2) years old, who were randomly divided into three groups with 21 in each. Patients in group I received heparin, propranolol with monopril and PCI; II--methylase (tenakteplaza) and propranolol, monopril and after 1 day they performed PCI; group III patients performed only PCI. With the help of echocardiography and Doppler echocardiometry values studied endsystolic (ESV) and end-diastolic (EDV) volume, ejection fraction (EF), stroke (SI) and heart (HI) index, index of local contractility disturbance of the left ventricle (LV ILCD) as well as the dynamics of systolic, (SBP) and diastolic (PBP) blood pressure, clinical features of myocardial infarction during follow-up. Injection of methylase, infusion of propranolol, receiving per os of monopril and conduct after 1 day of PCI accelerate the stabilization of central hemodynamics. ESV, EDV and ILCD reduce, systolic function of LV improves, ejection fraction increases. When there was no restenosis, myocardial infarction relapse and mortality 1 patient on 5th day was recorded acute heart failure (AHF). When treating by monopril, propranolol and heparin and conduct of PCI also stabilize central hemodynamics. ESV, EDV and ILCD reduce, EF increases and systolic function of LV improves (I group). However, in one patient on the 3rd day were recorded acute heart failure (AHF). Restenosis, recurrent myocardial infarction, and mortality were not observed. During the PCI only treatment 4 patients relapsed MI, 4 patients had restenosis, 2 patients had AHF and 2 patients died. Observations have shown that the combined application of drug therapy with PCI provides a positive predictive as opposed to using only PCI.

TLR4-mediated anti-atherosclerosis mechanisms of angiotensin-converting enzyme inhibitor--fosinopril.

Recently, angiotensin-converting enzyme inhibitor (ACEI) has gained increasing attention for its anti-atherosclerosis activity, but the underlying mechanism is unknown. In our study, we used rabbits fed with high-fat forage, as an atherosclerosis model to investigate the effect of fosinopril, which is an ACEI. Animals which received both high-fat forage and fosinopril, were maintained as the drug-treated group. Ultrasonography and Sudan III staining were used to determine the process of atherosclerosis. The expression of TLR4 and activity NF-κB were determined using western blot, RT-PCR and ELISA. The results showed that the atherosclerotic plaque was visible at sixteen weeks. More importantly, the atherosclerotic plaque was significantly decreased after fosinopril treatment. In the atherosclerosis model, the levels of TLR4 and NF-κB were increased, but this increased expression was inhibited in the fosinopril treated group. Our results demonstrated that TLR4 could be used as a potential biomarker for atherosclerosis and ACEI has the potential to be a new anti-atherosclerotic drug.

Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

Plasma Fibroblast Growth Factor 23 as a Predictor for Fosinopril Therapeutic Efficacy in Pediatric Primary Hypertension.

Background Plasma fibroblast growth factor 23 (FGF23) has been reported to be a predictive biomarker for therapeutic effectiveness of angiotensin-converting enzyme inhibitors in heart failure. Higher plasma FGF23 levels have been shown in pediatric primary hypertension, but the predictive value of FGF23 for angiotensin-converting enzyme inhibitors' effectiveness in pediatric primary hypertension has not been documented. Methods and Results This is a prospective study. An exploratory study with 139 patients was first conducted to determine the cutoff value of FGF23 for the prediction of treatment responsiveness. After receiving fosinopril for 4 weeks, of all 139 patients, 91 responded, while 48 did not respond to the treatment, and the responders had a significantly higher baseline plasma FGF23 level than nonresponders (P<0.01). Multiple regression analysis revealed a significant impact of baseline plasma FGF23 levels on fosinopril responsiveness (P<0.05). The receiver operating characteristic curve analysis showed that the plasma FGF23 predicted the effectiveness of fosinopril treatment with an area under the curve of 0.784 (95% CI, 0.704-0.863) for a sensitivity and a specificity of 67.0% and 89.6%, respectively, for a cutoff value of 62.08 RU/mL. Subsequently, another group of 40 patients were recruited for validation. The blood pressure control rate in those (n=22) with baseline plasma FGF23 >62.08 RU/mL was significantly higher than that in children (n=18) with FGF23 ≤62.08 RU/mL (P<0.05). Conclusions Plasma FGF23 might be a valuable biomarker to guide fosinopril therapy for primary hypertension in children.

Zerumbone, a humulane sesquiterpene from Syringa pinnatifolia, attenuates cardiac fibrosis by inhibiting of the TGF-ß1/Smad signaling pathway after myocardial infarction in mice.

BACKGROUND: Zerumbone (ZER) is a humulane sesquiterpene isolated from Syringa pinnatifolia Hemsl., a representative Mongolian herbal medicine that is used to treat cardiovascular diseases. Cardiac fibrosis is a common pathological process in cardiovascular disease that results from the excessive accumulation of extracellular matrix (ECM), and the transforming growth factor (TGF)-ß/Smad pathway is a canonical signaling pathway that directly induces expressions of ECM-related genes. Currently, the cardioprotective effect and underlying mechanisms of ZER on the inhibition of cardiac fibrosis are not well known. PURPOSE: To explore the cardioprotective properties and pharmacological mechanism of ZER against cardiac fibrosis via the TGF-ß1/Smad signaling pathway. METHODS: Myocardial infarction (MI) model was induced by ligation of the left anterior descending coronary artery in ICR mice. The mice were randomly divided into six groups: sham, model, low-dose ZER (ZER-L), medium-dose ZER (ZER-M), high-dose ZER (ZER-H) and fosinopril. Mice in each group were intragastrically administered treatments for 21 days, and cardiac function was evaluated by 2D echocardiography. The pathological structure of the heart was examined by hematoxylin and eosin (HE) and Masson staining. Content of collagen I and collagen III were assessed by immunofluorescence methods. The inhibitory effect of ZER on TGF-ß1 protein expression was predicted by molecular docking technology. Reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting were used to measure the levels of genes and proteins expressed in the TGF-ß1/Smad signaling pathway and MMPs. TGF-ß1-treated cardiac fibroblasts (CFs) of neonatal SD rats were adopted for in vitro studies. RESULTS: Cardiac ejection fraction (EF) and fractional shortening (FS) in the model group were markedly decreased compared with those in the sham group, indicating that the MI model was successfully established. ZER and fosinopril elevated EF and FS values, suggesting cardioprotective effects. Pathological staining and immunofluorescence analysis showed that the content of collagen I and collagen III increased in the cardiac tissue of mice in model group, while ZER treatment obviously reduced collagen levels. The molecular docking simulations predicted the hydrophobic interactions between ZER and TGF-ß1. In addition, the expression of TGF-ß1, p-Smad2/3 and MMPs in the ZER treatment group was significantly decreased compared with the model group. In vitro studies further confirmed that α-smooth muscle actin (α-SMA) and p-Smad2/3 increased markedly in cardiac fibroblasts after incubation with TGF-ß1, and treatment with ZER suppressed the expression of α-SMA and TGF-ß1 downstream proteins in cardiac fibroblasts. CONCLUSION: ZER rescues cardiac function by attenuating cardiac fibrosis, and the antifibrotic effect may be mediated by blocking the TGF-ß1/Smad pathway.

Antihypertensive drug treatment in white-coat hypertension: data from the Plaque HYpertension Lipid-Lowering Italian Study.

AIM: Little evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection might be indirectly inferred, however, from the blood pressure (BP) effects of treatment as in trials BP reduction is linearly related to outcome reduction. We analyzed the effect of antihypertensive treatment on office and ambulatory BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS). METHODS: : Office and ambulatory blood pressure were measured in 470 hypertensive patients randomized to fosinopril or hydrochlorothiazide alone or combined with a statin before treatment and at 6 month or yearly intervals during 2.6 years of follow-up. Patients were divided into two groups according to whether before randomization to treatment office and 24-h mean BP were elevated (sustained hypertension) or office BP was elevated but 24-h BP values were normal (WCH). RESULTS: : In both sustained hypertension and WCH antihypertensive treatment was associated with an early marked office BP reduction, which persisted virtually unchanged throughout the treatment period. In contrast, 24-h (and day and night) BP showed a marked and persistent treatment-related fall in sustained hypertension but no change in WCH. The results were similar when data were separately analyzed in patients under fosinopril or diuretic, with or without statin treatment. CONCLUSION: : In WCH, antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline. This appears to be unrelated to the type of treatment employed.

Long-term effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria:Ten years of follow-up of Prevention of Renal and Vascular End-stage Disease Intervention Trial (PREVEND IT).

BACKGROUND: The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion (UAE) would reduce adverse cardiovascular events. We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE >15 mg per 24 hours. METHODS: The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years. For every survivor, the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national databases and electronic hospital systems. RESULTS: Mean total follow-up of the extended PREVEND IT was 9.5 years (range 9.4-10.7 years). Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo (hazard ratio 0.87, 95% CI 0.61-1.24 [P = .42]) during long-term follow-up. After 9.5 years, subjects with a baseline UAE in the upper quintile (>50 mg/24 hours) had a total event rate of 29.5% and were at a higher risk for developing cardiovascular disease compared with less UAE (hazard ratio 2.03, 95% CI 1.38-2.97 [P ≤ .01]). In addition, 4 years of fosinopril treatment resulted in a risk reduction of 45% (95% CI 6%-75% [P = .04]) in this group compared with placebo. Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point (P = .99). CONCLUSIONS: Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up, with a doubling of the risk if the UAE is >50 mg per 24 hours. In this group, the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity. We propose that UAE be used to estimate risk in the general population and that large clinical trials be designed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities.

Fosinopril and losartan regulate klotho gene and nicotinamide adenine dinucleotide phosphate oxidase expression in kidneys of spontaneously hypertensive rats.

BACKGROUND/AIMS: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR). METHODS: Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-ß-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated. RESULTS: As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression. CONCLUSION: Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage.

Prostaglandin E1 for preventing the progression of diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is one of the major chronic microvascular complications in diabetes mellitus, and may progress to end-stage kidney disease (ESKD). There are no definitely effective approaches for preventing, delaying or treating DKD. Small studies have shown that Prostaglandin E1 (PGE1) can improve renal blood circulation and decrease proteinuria and albuminuria. OBJECTIVES: To assess the benefits and harms of PGE1 for preventing the progression of DKD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedicine Database (CBM) and reference lists of articles with no language restriction. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs comparing any PGE1 agent used for preventing the progression of DKD, regardless of dosage, mode of administration, addition of cointerventions or duration of treatment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. For dichotomous outcomes (all-cause mortality, ESKD), results were expressed as relative risk (RR) with 95% confidence intervals (CI). Continuous outcomes (microalbuminuria, proteinuria, albuminuria, doubling of serum creatinine, serum creatinine) were expressed as mean difference (MD) with 95% CI. MAIN RESULTS: Six studies (271 patients) were included. Five studies investigated PGE1 with or without fosinopril/losartan versus fosinopril/losartan or no treatment and one compared PGE1 versus Xueshuantong (a Chinese medicinal herb). There was a significant decrease in urinary albumin excretion rate (UAER) in patients treated with PGE1 (MD -48.28 microg/min, 95% CI -75.29 to -21.28), other outcomes also showed a significant decrease in the patients with PGE1 (albuminuria: MD -143.66 mg/24 h, 95% CI -221.48 to -65.84; proteinuria: MD -300 g/24 h, 95% CI -518.34 to -81.66). PGE1 had a positive effect on albuminuria (MD -660 mg/24 h, 95% CI -867.07 to -452.93) in clinical DKD (CDN, III stage of DN) compared with Xueshuantong. No data on incidence of ESKD, all-cause mortality or quality of life were available. AUTHORS' CONCLUSIONS: PGE1 may have positive effects on DKD by reducing UAER, decreasing albuminuria and lessening proteinuria, with no obvious serious adverse events. However, limited by the poor methodological quality of the included studies and the small number of participants, there is currently insufficient evidence for determining if PGE1 could be used for preventing the progression of DKD. Large, properly randomised, placebo-controlled, double-blind studies are urgently needed.

Effect of combined angiotensin-converting enzyme and aldosterone inhibition on plasma plasminogen activator inhibitor type 1 levels in chronic hypertensive patients.

AIM: A possible link between the renin-angiotensin-aldosterone system (RAAS) and fibrinolysis has recently been suggested. Systemic infusion of angiotensin II results in an increase in plasminogen activator inhibitor type 1 (PAI-1) levels and angiotensin-converting enzyme inhibitors (ACEI) have been shown to decrease PAI-1 levels. Moreover, recent data indicated that plasma aldosterone levels were positively correlated with plasma PAI-1 levels. This study was designed to compare the effects of an ACEI with an ACEI in combination with an aldosterone antagonist on PAI-1 levels in chronic hypertensive patients. METHODS: Patients were randomized into two groups and were treated with either low salt diet plus fosinopril (group 1, n = 43) or low salt diet plus fosinopril plus spironolactone (group 2, n = 42). Plasma PAI-1, tissue plasminogen activator (tPA) and plasma renin activity (PRA) levels were measured before and after 24 week treatment in both groups. RESULTS: The mean basal PRA levels were similar in both groups. After antihypertensive therapy, the mean PRA increased significantly in both groups (P < 0.005). The mean plasma PAI-1 levels were reduced in both treatment groups (P < 0.005). However, the reduction in group 2 was more pronounced (P < 0.05). Although after the treatment mean plasma levels of PAI-1 significantly reduced in both groups, the reduction of PAI-1 levels was more pronounced in group 2. CONCLUSION: Although the plasma levels of PAI-1 significantly reduced after treatment in both groups, the reduction of PAI-1 levels was more pronounced in group 2. These data indicated that administration of aldosterone antagonists in combination with ACEI had additional benefit on fibrinolysis in chronic hypertensive patients.

Effects of combination therapy with amlodipine and fosinopril administered at different times on blood pressure and circadian blood pressure pattern in patients with essential hypertension.

OBJECTIVE: The objective of our study was to compare the effects of a combination therapy with amlodipine and fosinopril administered concomitantly or at different times on blood pressure and circadian blood pressure pattern in subjects with essential hypertension. METHODS: 40 subjects with grade 1-2 essential hypertension and uncontrolled blood pressure after amlodipine or fosinopril monotherapy were randomized to combination therapy with amlodipine and fosinopril given in the morning and at bedtime (group A), or given concomitantly in the morning (group B). Clinic blood pressure values and 24-hour ambulatory blood pressure measurements were obtained before and after 4 weeks of treatment. RESULTS: After treatment, a reduction of 24-hour mean systolic and diastolic blood pressure was found in both groups. Subjects in group A showed a significant reduction in mean nocturnal systolic and diastolic blood pressure compared with group B (22.38/17.39 mmHg vs. 7.61/6.32 mmHg; P < 0.001). In group A a significant increase (5.68% and 4.57%, respectively; P < 0.05) was found in the diurnal/nocturnal blood pressure ratios of systolic and diastolic blood pressure and a slight reduction in the prevalence of non-dipping (< 10% decline in mean nocturnal vs. diurnal BP) from 53.85% to 30.77% (P = 0.428). Group B showed a significant reduction (5.68% and 5.76%; P < 0.01) in the diurnal/nocturnal systolic and diastolic blood pressure ratios and a slight increase in the prevalence of non-dipping from 38.46% to 53.85% (P = 0.428). CONCLUSION: Compared to concomitant administration of amlodipine and fosinopril in the morning, administration of the drugs at different times significantly decreased nocturnal blood pressure, increased the diurnal/nocturnal blood pressure ratio, and normalized the circadian blood pressure pattern. These findings indicate that chronotherapy may be an important strategy for optimizing blood pressure control and restoring the circadian blood pressure pattern.

[Protective effect of fosinopril sodium pretreatment combined with ischemic postconditioning on rat heart underwent myocardial ischemia/reperfusion injury].

OBJECTIVE: To investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion. METHODS: Sixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA. RESULTS: Compared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01). CONCLUSION: Pretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.

Fabry disease with early-onset ventricular dilation: A case report.

RATIONALE: The most common cardiac involvement of Fabry disease (FD) is left ventricular hypertrophy (LVH), which usually occurs in male patients over the age of 30. In rare cases, it can progress to ventricular dilation in the late stage of the disease. PATIENT CONCERNS: A 16-year-old boy presenting with recurrent extremity pain and chest distress was admitted to our hospital. Imaging examinations revealed ventricular dilation. DIAGNOSIS: α-Galactosidase A enzyme assay and GLA gene sequencing confirmed the diagnosis of FD and revealed a novel mutation c.76_77insT. INTERVENTIONS: The patient was treated using metoprolol (23.75 mg qd) and angiotensin-converting enzyme inhibitor (fosinopril sodium 5 mg qd). He refused enzyme replacement therapy for financial reasons. OUTCOMES: The echocardiography, electrocardiography, renal function, and routine blood and urine tests performed 20 months after the patients discharge from hospital showed no significant changes. The patient reported a slow and gradual decrease in the frequency and degree of pain and chest distress, starting approximately 24 months after discharge. LESSONS: Cardiac involvement of FD can progress rapidly in some cases. Screening for FD should be considered in patients with unexplained ventricular dilation, especially in those with a history of typical FD manifestations.

Destruction of the blood-retina barrier in diabetic retinopathy depends on angiotensin-converting enzyme-mediated TGF-ß1/Smad signaling pathway activation.

Diabetes mellitus (DM) is a systemic, chronic metabolic disease that is related to heredity and autoimmunity and is often accompanied by complications of retinopathy. However, the causative mechanism involved in the pathological process remains unclear. In this research, treatment with fosinopril or LY2109761 was found to be responsible for the improvement of the pathological processes, serum biochemical indexes and retinopathy in rats with streptozotocin-induced diabetes. In addition, the upregulation of angiotensin-converting enzyme (ACE) in the serum and the increased expression of TGF-ß1 in the pathological outer nuclear layer (ONL) and inner nuclear layer (INL) of the retina were also reduced. In vitro experiments demonstrated that ACE enhanced cell damage and TGF-ß1/Smad signaling pathway activation in retinal capillary endothelial cells (RCECs) under high glucose conditions. In addition, the activity of ACE was also considered to be related to the increasing levels of activated TGF-ß1 in both rat retinal Müller cells (RMCs) and RCECs, but ACE activity had no effect on the high glucose-mediated upregulation of total TGF-ß1 in RMCs. Coculture experiments with RCECs and RMCs showed that the barrier that was established under normal conditions was significantly impaired when exposed to high glucose combined with ACE, and damage of barrier can be prevented by adding fosinopril or LY2109761. Finally, a similar auxiliary effect of ACE was also observed in the activated TGF-ß1-mediated barrier damage in blood-retinal barrier model in vitro. In summary, ACE-mediated TGF-ß1/Smad signaling pathway activation was found to be involved in the destruction of the blood-retina barrier during diabetic retinopathy in a model of streptozotocin-induced diabetes, and these data may provide evidence to guide the treatment of the complications of diabetes mellitus.

Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.

BACKGROUND: Beneficial effects of angiotensin-converting enzyme (ACE) inhibitors seem to be mediated by mechanisms that are partly independent of blood pressure lowering. The present study evaluates effects of an ACE inhibitor (ie, fosinopril) intervention on novel cardiovascular risk factors. METHODS: Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial enrolling subjects > or =55 years old with high cardiovascular disease risk profile. Biomarkers of hemostasis (ie, plasminogen activator inhibitor 1, D-dimer), inflammation (ie, C-reactive protein, interleukin-6), and endothelial function (ie, endothelin 1, vascular cell adhesion molecule 1) were measured at the baseline, at the midterm, and at end of follow-up (after 1 year) clinic visits. Paired t test analyses (after Sidak's adjustment, P < .009) were performed to compare biomarkers modifications after fosinopril/placebo interventions. RESULTS: Mean age of the sample (n = 290, women 43.4%) was 66.0 years old. No significant differences were reported for C-reactive protein, interleukin 6, plasminogen activator inhibitor 1, vascular cell adhesion molecule 1, and endothelin 1 levels in the comparisons between fosinopril and placebo interventions. D-dimer was the only biomarker showing a significant difference between fosinopril intervention (median 0.32 microg/mL, interquartile range 0.22-0.52 microg/mL) and placebo (median 0.29 microg/mL, interquartile range 0.20-0.47 microg/mL, P = .007) when analyses were restricted to participants with higher compliance to treatment and receiving the maximum ACE inhibitor dosage. CONCLUSIONS: Angiotensin-converting enzyme inhibition does not significantly modify major biomarkers of inflammation, hemostasis, and endothelial function. Further studies should confirm the possible effect of ACE inhibitors on the fibrinolysis pathway.

Primary gait ignition disorder: report of three cases.

Gait ignition failure (GIF) classifications all had major limitations. Few years ago, a new and simpler classification was proposed by Liston. The aim of this paper is to discuss three GIF patients with respect to this new classification. All three patients presented with hesitation to start walking and turning and their neurological examination revealed start and turn hesitation without any other abnormality. We classified our patients according to Liston's classification as ignition apraxia, which enabled us to approach the patients in a practical way. This classification helps to understand the underlying pathologies and combines clinical characteristics and pathophysiology. We reported our experience with pergolide in the treatment of patients suffering from primary GIF and underline the fact that more research is needed on the treatment of this condition.

[Fosinopril in the treatment of cardiorenal syndrome in chronic cardiac failure].

Renal dysfunction is an independent risk factor of chronic cardiac failure (CCF) and death due to this disease. CCF patients are elderly patients with diabetes mellitus, arterial hypertension and long-term chronic cardiac insufficiency. CCF patients do not often have left ventricular systolic dysfunction, renal affection is not associated with low ejection syndrome. Renal affection in CCF is primarily caused by activation of the system rennin-angiotensin, inflammation, disturbed bioavailability of nitric oxide, hyperactivation of the sympathetic nervous system. ACE inhibitors correct pathophysiological disorders of renal flow in CCF. Fosinopril shows the highest efficacy and safety in management of cardiorenal syndrome in CCF patients. Fosinopril can also prevent renal dysfunction in CCF patients.