enalapril and Brain-Ischemia

Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited.. We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients.. The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y.. There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18).. Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. This study was registered at clinicaltrials.gov as NCT00794885.

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Case-Control Studies; China; Double-Blind Method; Enalapril; Female; Folic Acid; Hemorrhage; Homocysteine; Humans; Hypertension; Male; Middle Aged; Odds Ratio; Primary Prevention; Risk Factors; Stroke; Vitamin A; Vitamin A Deficiency

Over 80% of patients exhibit an acute increase in blood pressure (BP) following stroke. Current clinical guidelines make no distinction in BP management between patients with or without prior hypertension. Spontaneously hypertensive (SH) rats were preinstrumented with telemeters to record BP, intracranial pressure, and brain tissue oxygen in the predicted ischemic penumbra for 3 days before and 10 days after transient middle cerebral artery occlusion (n=8 per group) or sham (n=5). Before stroke, BP was either left untreated or chronically treated to a normotensive level (enalapril 10 mg/kg per day). Poststroke elevations in BP were either left uncontrolled, controlled (to the prestroke baseline level), or overcontrolled (to a normotensive level) via subcutaneous infusion of labetalol. Baseline values of intracranial pressure and brain tissue oxygen were similar between all groups, whereas BP was lower in treated SH rats (144±3 versus 115±5 mm Hg;

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Brain; Brain Chemistry; Brain Ischemia; Enalapril; Hypertension; Infarction, Middle Cerebral Artery; Intracranial Hypertension; Male; Movement Disorders; Oxygen; Random Allocation; Rats; Rats, Inbred SHR; Recovery of Function; Time Factors

Posterior reversible encephalopathy syndrome (PRES) and cerebral sinus thrombosis are 2 known complications of acute lymphoblastic leukemia and its treatment. We describe a patient with acute lymphoblastic leukemia whose course was complicated by both of these conditions. This case is novel both for the fact that PRES developed before the initiation of therapy and that PRES was followed shortly by the development of cerebral sinus thrombosis. Our patient's story raises questions about our current understanding of the pathophysiology of PRES, and it suggests that PRES may actually be a predisposing risk factor for cerebral sinus thrombosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Ischemia; Cerebral Infarction; Child, Preschool; Enalapril; Enoxaparin; Female; Humans; Intracranial Hypertension; Magnetic Resonance Imaging; Neuroimaging; Occipital Lobe; Papilledema; Parietal Lobe; Posterior Leukoencephalopathy Syndrome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Sinus Thrombosis, Intracranial

1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. Vehicle and a non-hypotensive dose of enalapril (0.03 mg/kg) were administered at the beginning of the reperfusion period. A neurological deficit score (NDS) was determined for all rats at the end of the reperfusion period. Then, brain oedema formation was investigated using the wet-dry weight method and BBB permeability was evaluated on the basis of extravasation of Evans blue (EB) dye. In addition, oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA) in brain homogenates. 3. Inhibition of ACE by enalapril significantly reduced NDS and decreased brain oedema formation (P < 0.05 for both). Disruption of the BBB following ischaemia resulted in considerable leakage of EB dye into the brain parenchyma of the ipsilateral hemispheres of vehicle-treated rats. Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Cerebral Arteries; Enalapril; Glutathione; Male; Malondialdehyde; Oxidative Stress; Permeability; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Central renin angiotensin system has an important role on the cerebral microcirculation and metabolism. Our previous work showed that inhibition of angiotensin converting enzyme (ACE) activity prior to induction of ischemia protected the brain from severe ischemia/reperfusion (I/R) injuries. This study evaluated the impacts of post-ischemic inhibition of ACE, enalapril, on brain infarction in normotensive rats.. Rats were anesthetized with chloral hydrate (400 mg/kg). Focal cerebral ischemia was induced by 60-min intraluminal occlusion of right middle cerebral artery (MCA). Intraperitoneal injection of enalapril (0.03 or 0.1 mg/kg) was done after MCA reopening (reperfusion). Neurological deficit score (NDS) was evaluated after 24 h and the animals randomly assigned for the assessments of infarction, absolute brain water content (ABWC) and index of brain edema.. Severe impaired motor functions (NDS = 2.78 ± 0.28), massive infarction (cortex = 214 ± 19 mm3, striatum = 86 ± 5 mm3) and edema (ABWC = 83.1 ± 0.46%) were observed in non-treated ischemic rats. Non-hypotensive dose of enalapril (0.03 mg/kg) significantly reduced NDS (1.5 ± 0.22), infarction (cortex = 102 ± 16 mm3, striatum = 38 ± 5 mm3) and edema (ABWC = 80.9 ± 0.81%). Enalapril at dose of 0.1 mg/kg significantly lowered arterial pressure could not improve NDS (2.0 ± 0.45) and reduce infarction (cortex = 166 ± 26 mm3, striatum = 71 ± 11 mm3).. Post-ischemic ACE inhibition in the normotensive rats without affecting arterial pressure protects the brain from reperfusion injuries; however, this beneficial action is masked by hypotension.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Enalapril; Free Radicals; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The influence of vinpocetine, pentoxifylline and enalapril on endothelium functions has been studied in a group of in 172 patients with chronic brain ischemia. The endothelium-protective effect of drugs was manifested as the inhibition of the Willebrand factor output during arteriovenous occlusion test and as the renewal of endothelium-depended vasodilation. The extent of neurologic deficit reduction correlated with decrease in the activated endothelium-depended output of the Willebrand factor.

Topics: Adult; Aged; Antihypertensive Agents; Brain Ischemia; Case-Control Studies; Cerebrovascular Circulation; Cholesterol; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Fibrinogen; Humans; Middle Aged; Pentoxifylline; Treatment Outcome; Vasodilation; Vasodilator Agents; Vinca Alkaloids; von Willebrand Factor

The study included 56 patients with chronic cerebral ischemia and arterial hypertension. Protective effect of enalapril (enap) on endothelium was apparent as increased fibrinolytic activity of plasma, decreased platelet aggregation amplitude caused by adrenalin and ristocetin, partial restoration of endothelium-dependent vasodilation, and inhibition of Willebrand factor release in the arteriovenous occlusion test. The degree of reduction of neurologic deficit by enalapril correlated with the decrease in Willebrand factor release.

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Chronic Disease; Drug Administration Schedule; Enalapril; Endothelium, Vascular; Humans; Hypertension; Middle Aged; Treatment Outcome; von Willebrand Factor

There is evidence that acutely elevated blood pressure (BP) after stroke is associated with increased cerebral hemorrhage and edema. Previous experiments in our laboratory have shown that candesartan 1 mg/kg administered after reperfusion in a model of hypertension after experimental ischemic stroke reduces neurovascular damage and improves outcome. These results could be either mediated by BP lowering or a BP-independent cerebrovascular protective effect.. To determine the contribution of BP lowering to the neurovascular protection previously reported with candesartan after stroke.. Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either hydralazine 1 mg/kg (n = 8), enalapril 5 mg/kg (n = 7) or enalapril 10 mg/kg (n = 8) were administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. After neurological function was assessed, brain tissue was processed for infarct size and hemoglobin content analyses.. Mean arterial pressure (MAP) increased from 92 to 124 mmHg immediately upon MCAO and decreased to 112 mmHg after reperfusion, remaining elevated for 24 h (P < 0.0001) in the saline group. Hydralazine reduced MAP (P = 0.048) and infarct size (53 versus 30%, P = 0.0083), and there was a trend towards decreased hemoglobin content. Enalapril 5 mg/kg did not significantly change MAP or other outcomes. Enalapril 10 mg/kg reduced MAP (P < 0.0001) and infarct size (53 versus 29%, P = 0.003). There was an intermediate effect on both hemoglobin content and neurological function, neither one was significant. The time course of BP lowering varied with each treatment.. Acute BP lowering after reperfusion in acute ischemic stroke is an effective strategy to achieve neurovascular protection. The rate, extent and mechanism of BP lowering may determine the magnitude of protection.

Topics: Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Area Under Curve; Benzimidazoles; Biomarkers; Biphenyl Compounds; Blood Pressure; Brain Ischemia; Cerebrovascular Circulation; Circadian Rhythm; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Hemoglobins; Hydralazine; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Wistar; Reperfusion; Telemetry; Tetrazoles

The effects of an angiotensin II type 1 (AT1) receptor blocker (ARB) on ischemic brain damage induced by middle cerebral artery (MCA) occlusion were compared with those of an angiotensin converting enzyme (ACE) inhibitor. Treatment of male C57BL/6J mice with an ARB, candesartan, reduced the brain ischemic area and neurological deficit after MCA occlusion at a non-hypotensive dose. In contrast, an ACE inhibitor, enalapril, did not reduce the brain ischemic area, and neurological deficit even at a hypotensive dose. Candesartan improved the reduction of brain surface blood flow after MCA occlusion, and inhibited the increase in superoxide production both in the cortex and brain arterial wall at non-hypotensive and hypotensive doses. However, enalapril did not affect the changes in blood flow and superoxide production in the brain after MCA occlusion. AT2 receptor expression in the ischemic area was increased at 3 h after MCA occlusion by pretreatment with candesartan, but not that with enalapril. AT1 receptor expression was neither affected by candesartan nor by enalapril. These results suggest that candesartan attenuated ischemic brain damage, at least partly, through inhibition of oxidative stress.

Topics: Analysis of Variance; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Brain; Brain Ischemia; Cerebrovascular Circulation; Dose-Response Relationship, Drug; Enalapril; Histocompatibility Antigens; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Superoxides; Tetrazoles; Tetrazolium Salts

The purpose of our research was to study the pattern of post-ischemic cerebral hemodynamic changes and observe the impact of enalapril on the course of these changes in cats.. The experiments were carried out on anesthetized cats using the autohemoperfusion method in cerebral and peripheral vessels with a stable volume of blood. Transitional peripheral (lower limb) and brain ischemia was simulated by stopping the autohemoperfusion pump for 15 minutes, tying various anastomoses in the neck region, and reducing arterial blood pressure (ABP) to 40-30 mm Hg, followed by reinfusion of the shed blood.. Intravenous administration of enalapril solution in a dosage of 0.25 mg kg-1 in the early phase of reperfusion (10 minutes into the postischaemic period) prevented the development of long-term "no-reflow"of cerebral blood flow, as observed in the controls. There was a 40.8+/-3.2% reduction of cerebrovascular tone, 39.3+/-3.1% in peripheral vessels, and 44.7+/-1.5% lower arterial blood pressure at the end of 120 minutes.. Enalapril caused a reduction of cerebrovascular tone, completely eliminating the "no-reflow" syndrome after brain ischemia and somewhat potentiated the hyperperfusion phase. At the same time, the drug did not aggravate the general hypotension observed after ischemia in the controls.

Topics: Animals; Arteriovenous Anastomosis; Brain; Brain Ischemia; Cats; Cerebrovascular Circulation; Enalapril; Extremities; Ischemia

This consensus is the result of a recent meeting to establish the ideal approach for thrombolysis in acute stroke patients in Brazil. Some peculiarities concerning the emergency rooms, stroke units, available equipments and stroke teams are considered in order to characterize the stroke centers. Protocols concerning the use of thrombolytic drugs are reviewed. This is the official guideline for thrombolysis in acute stroke of the Brazilian Society of Cerebrovascular Disease.

Topics: Acute Disease; Brain Ischemia; Brazil; Enalapril; Fibrinolytic Agents; Humans; Metoprolol; Stroke; Thrombolytic Therapy

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Brain Ischemia; Disease Models, Animal; Enalapril; Gerbillinae; Lisinopril; Losartan; Male; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Reproducibility of Results; Stroke; Tetrazoles

Angiotensin-converting enzyme inhibitors have been demonstrated to protect spontaneously hypertensive rats from cerebral ischemia. The present study investigated the protective effect of enalapril and moexipril in models of permanent focal cerebral ischemia in normotensive mice and rats. To elucidate the mechanism of neuroprotection the influence of these angiotensin-converting enzyme inhibitors on glutamate-, staurosporine- or Fe2+/3+-induced generation of reactive oxygen species and neuronal cell death in primary cultures from chick embryo telencephalons was studied. Treatment with moexipril or enalapril dose-dependently reduced the percentage of damaged neurons, as well as mitochondrial reactive oxygen species generation induced by glutamate, staurosporine or Fe2+/3+. Furthermore, moexipril and enalapril attenuated staurosporine-induced neuronal apoptosis as determined by nuclear staining with Hoechst 33258. In mice, 1 h pretreatment with enalapril (0.03 mg/kg) or moexipril (0.3 mg/kg) significantly reduced brain damage after focal ischemia as compared to control animals. Additionally, moexipril (0.01 mg/kg) was able to reduce the infarct volume in the rat model after focal cerebral ischemia. The results of the present study indicate that the angiotensin-converting enzyme inhibitors enalapril and moexipril promote neuronal survival due to radical scavenging properties.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Arterial Occlusive Diseases; Blood Pressure; Brain; Brain Ischemia; Carcinogens; Cells, Cultured; Cerebral Arteries; Chick Embryo; Dose-Response Relationship, Drug; Enalapril; Ferric Compounds; Ferrous Compounds; Free Radical Scavengers; Free Radicals; Glutamic Acid; Isoquinolines; Male; Mice; Mice, Inbred Strains; Neurons; Neuroprotective Agents; Rats; Rats, Long-Evans; Staurosporine; Tetrahydroisoquinolines

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Brain Ischemia; Captopril; Cerebral Cortex; Enalapril; Neuroprotective Agents; Rats