Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain metabolites and arterial acid-base measurements were made one hr after bilateral carotid artery occlusion in 2 different models of hypertensive rats. Animals used included renovascular hypertensive rats (RHR) with an altered renin-angiotensin system and desoxycorticosterone hypertensive rats (DHR) with low plasma renin activity (PRA). The mean value for supratentorial lactate of 7.41 mM/kg in RHR was significantly higher than in DHR (3.90 MM/kg) or in control normotensive rats (3.10 - 2.56 mM/kg). Concomitantly, the lactate/pyruvate ratio tended to increase and ATP to decrease in RHR only. In these same rats (RHR) infratentorial lactate was also increased. The results suggest that bilateral carotid occlusion leads to anaerobic metabolism of the brain in RHR but not in DHR, suggesting that the renin-angiotensin system may play some role in the susceptibility to cerebral ischemia following carotid occlusion in the hypertensive rats.
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PMID:Brain metabolism following bilateral carotid occlusion in 2 different models of experimental hypertensive rats. 50 99

The angiotensin converting enzyme (ACE) inhibitor captopril proved to be an effective antihypertensive drug during a 5-year follow-up study of patients with severe hypertension who had been resistant to a triple-drug regimen. Of the 42 patients, 41 had to be treated additionally with diuretics. Because of hypokalemia, potassium supplements were necessary in 26 patients, despite the use of "potassium-saving" diuretics in 12 patients. Blood pressure was controlled sufficiently in 3/4 of the patients during the 5 years. Patients with a large elevation in plasma renin activity showed the best response to the treatment. Six patients died during the 5 years. Therapy had to be stopped in 11 patients because of complications. The following complications and adverse effects were observed: cerebral ischemia (n = 10), vertigo and orthostasis (10), exanthema (9), hypogeusia (7), circulatory failure (7), myocardial infarction (6), and scintigraphically demonstrable decrease of renal perfusion (5). One patient with bilateral renal artery stenosis suffered from acute renal failure, which was reversible after withdrawal of captopril. Significant changes of red and white blood cell counts, transaminases, lipids, urine protein excretion, and heart rate were not observed.
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PMID:[Results of a 5-year study with captopril in patients with severe therapy-resistant hypertension]. 302 Mar 11

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
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PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

Recently, several antagonists of angiotensin II receptors (AII-A) have been developed and are now used as antihypertensive agents. The regional cerebral blood flow appears to show typical changes during the course of cerebral ischemia and AII-A may have a favorable effect on the flow in some situations. Moreover, activation of the renin-angiotensin system plays an important role in the development of cerebrovascular lesions in chronic hypertension. Because several enzymes appear to produce angiotensin II in the absence of classical renin-angiotensin system, it is possible that angiotensin II is produced in some blood vessels even after inhibition of the activity of ACE. Thus, AII-A may be more effective to treat cerebrovascular lesions during hypertension than ACE inhibitors.
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PMID:[Angiotensin II receptor antagonists as the agents to treat cerebrovascular disease]. 1041 76

Subarachnoid haemorrhage is a serious condition often accompanied by delayed cerebral ischaemia. Earlier reports have provided evidence suggesting a role for angiotensin II in the development of cerebral vasospasm following subarachnoid bleeding. We sought to examine the influence of angiotensin II blockade with losartan on blood pressure and survival in animals following experimental subarachnoid haemorrhage, induced in conscious rats by injecting homologous blood via a catheter placed along the surface of the brain. We combined measurements of plasma renin activity with blood pressure recording in order to examine renin-angiotensin system activation following experimental subarachnoid haemorrhage. Following subarachnoid injury an approximately three-fold increase in plasma renin activity occurred (3.4 +/- 1.0 vs. 10.1 +/- 1.8 ng angiotensin I produced/ml/h, p < 0.01). In animals treated with losartan (20 mg/kg) prior to the induction of subarachnoid haemorrhage blood pressure fell dramatically following the cerebral injury (124 +/- 5 vs. 94 +/- 7 mmHg, p < 0.001), whereas blood pressure remained unchanged in control animals. Survival was markedly reduced in those animals treated with losartan. Given the pronounced decrease in blood pressure and impaired survival following subarachnoid haemorrhage in animals treated with losartan, it would appear that the acute activation of the renin-angiotensin system following this insult is in fact a desirable, compensatory response.
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PMID:Beneficial effect of renin-angiotensin system for maintaining blood pressure control following subarachnoid haemorrhage. 1053 31

Experimental and clinical studies have proved an important role of the reaction of a stress-realizing endocrine system for both a course and an outcome of acute somatic diseases. That is why plasma concentrations of thyroxine (T4), triiodo-thyronine (T3), thyrotropic (TTH) and adrenocorticotropic (ACTH) hormones as well as of renin were measured during the 1-st week of acute ischemic stroke (AIS) in relevant patients for determination of their prognostic significance. 16 patients with hemispheric AIS were examined. A complex clinical biochemical investigation performed in patients with acute disorders of cerebral circulation revealed the presence of the "low T3 syndrome" accompanied by an increase of blood plasma levels of T4 by the 7-th day of the disease as well as an increase of the concentrations of TTH, ACTH and renin on the 2-nd day of the stroke. That reflected the severity of cerebral ischemia. Close correlation observed between the degree of normalization of hormonal concentrations and manifestations of neurologic disorders' regression by the 7-th and the 21-st days gave a good ground to consider these indices as a prognostic criterion for determination of an outcome of the acute period of ischemic stroke.
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PMID:[The influence of hormones of stress-promoting system on the course of acute ischemic stroke]. 1081 66

Strokes have been known since ancient times. Today, stroke is the second most frequent cause of death and the most frequent cause of invalidity. In about 80% of cases, stroke is caused by cerebral ischemia and in about 20% by intracerebral hemorrhage, subarachnoidal hemorrhage, venous thrombosis and other cerebrovascular diseases. The brain is one of the most richly perfused tissues and depends fundamentally on the supply of oxygen and glucose. In order to assure adequate cerebral blood flow, the brain is capable of autoregulation through the interaction of diverse autoregulatory mechanisms (myogenic, neurogenic and metabolic factors, blood viscosity, renin-angiotensin-system and endothelium). Reduction of cerebral blood flow below the threshold of about 25 ml/100 g x min leads to an impairment of the functional metabolism and later to impairment of the structural metabolism. Pathophysiologically, a large number of isolated pathobiochemical processes (loss of energy, lactate acidosis, excitating amino acid release, ion balance disorders, calcium overload, free radical release, etc.) start to interfere with each other. Delayed edema and inflammation lead to secondary brain damage. Apoptosis is probably induced by ischemia and can cause secondary deterioration. The basic principles in the treatment of ischemia are firstly the rapid restoration of cerebral blood flow (lysis, carotid endarterectomy) and secondly--following infarction--a limitation of brain damage (preservation of ischemic but not necrotic brain tissue, prevention of secondary complications). Stroke treatment requires profound diagnostic and therapeutic expertise and interdisciplinary cooperation of neuroradiologists, neurosurgeons, vascular surgeons and cardiologists. Stroke can best be managed in special "stroke units", which have now been established in nearly all parts of Germany. Beside acute management of stroke and neurological rehabilitative treatment, emphasis has to be laid on primary (public information, education, treatment of risk factors) and secondary prophylaxis (treatment with antiaggregants, anticoagulants, a. o.).
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PMID:[Cerebrovascular circulation from a clinical view. Historical review, physiology, pathophysiology, diagnostic and therapeutic aspects]. 1171 30

Since pharmacological interactions of the renin-angiotensin system appear to alter the neurological outcome of stroke patients significantly, we examined the effect of elevated levels of angiotensin II and the role of its receptor subtype AT1 in brain infarction in transgenic mice after focal cerebral ischemia. Angiotensinogen-overexpressing and angiotensin receptor AT1 knockout mice underwent 1 h or 24 h permanent middle cerebral artery occlusion (MCAO). The current study revealed a much smaller penumbra size, i.e., brain tissue at risk, in angiotensinogen-overexpressing animals compared with their wild-type subgroup after 1 h MCAO, but an enlarged infarct size after 24 h. In contrast, a smaller lesion area of energy failure and a much larger penumbral area were found in AT1 knockout mice compared with wild-type littermates. Lower perfusion thresholds for ATP depletion and protein synthesis inhibition after MCAO in AT1-deficient mice and reduced cell damage in an in vitro model using embryonic neurons of AT1 knockout mice suggest injury mechanisms independent of arterial blood pressure. Our data, therefore, demonstrate a direct correlation between brain angiotensin II and the severity of ischemic injury in experimental stroke.
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PMID:Ischemic injury in experimental stroke depends on angiotensin II. 1181 64

Stroke has enormous clinical, social, and economic implications, and demands a significant effort from both basic and clinical science in the search for successful therapies. Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process. Complex interactions occur between the classic risk factors for atherosclerosis and its clinical consequences. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist.
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PMID:Inflammation and infection in clinical stroke. 1246 86

Several lines of clinical and experimental evidence suggest an important role of the renin-angiotensin system in ischemic brain injury although the cellular regulation of the angiotensin AT1 and AT2 receptors and their potential relevance in this condition have not yet been clearly defined. We first assessed the regulation of brain AT1 and AT2 receptors in response to transient unilateral medial cerebral artery occlusion in rats by real-time RT-PCR, Western blot, and immunofluorescence labeling. AT2 receptors in the peri-infarct zone were significantly upregulated 2 days after transient focal cerebral ischemia. Increased AT2 receptors, which were abundantly distributed in a large number of brain regions adjacent to the infarct area including cerebral frontal cortex, piriform cortex, striatum, and hippocampus, were exclusively expressed in neurons. By contrast, AT1 receptors, which remained unaltered, were mainly expressed in astrocytes. In neurons of ischemic striatum, increased AT2 receptors were associated with intense neurite outgrowth. Blockade of central AT2 receptors with PD123177 abolished the neuroprotective effects of central AT1 receptor blockade with irbesartan on infarct size and neurological outcome. In primary cortical neurons, stimulation of AT2 receptors supported neuronal survival and neurite outgrowth. Our data indicate that cerebral AT2 receptors exert neuroprotective actions in response to ischemia-induced neuronal injury, possibly by supporting neuronal survival and neurite outgrowth in peri-ischemic brain areas.
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PMID:Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury. 1566 34


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