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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renin angiotensin aldosterone system (RAAS) in the central nervous system (CNS) and therapeutical effects of angiotensin II receptor blockers (ARBs) have been highlighted. In stroke, clinical trials exhibit to prevent primary onset or recurrence of stroke beyond anti-hypertensive effect, inhibition of atrial fibrillation and diabetes mellitus. ARB could be also expected to prevent cognitive impairment induced by such as Alzheimer disease, stroke and metabolic syndrome; however, clinical evidence has not been revealed to date. Angiotensin II levels in cerebrospinal fluid in patients with neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis is reduced, suggesting the role of RAAS in neural intractable diseases. These findings will provide us new therapeutic approaches of ARB in CNS disorder in t hefuture.
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PMID:[New insights of ARB in central nervous system]. 1934 36

Angiotensin II plays an important role in the cardiovascular continuum starting with risk factors and progressing to atherosclerosis, target organ damage, and ultimately to heart failure, stroke, or death. Inhibiting the renin-angiotensin-aldosterone system (RAAS) represents a cornerstone for the treatment of hypertension and heart failure. In patients with heart failure, the single RAAS blockade with angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce morbidity and mortality, increase life expectancy, and preserve the renal function. AT1 receptor blockers (ARBs) are equally effective in reducing mortality and morbidity in patients with impaired left ventricular function. The combination of ACE inhibitors with ARBs leads to an additive blood pressure lowering effect, better reduction in proteinuria, and to additive benefits in heart failure and left ventricular hypertrophy. But combination therapy is also associated with more side effects. Further investigations evaluating the effect of dual RAAS blockade on fatal and nonfatal cardiovascular events are needed.
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PMID:Dual blockade versus single blockade of the renin-angiotensin system in the light of ONTARGET. 1949 15

Angiotensin II (Ang II) receptor blockade is beneficial in stroke, possibly due to attenuation of vascular oxidative stress. Mice genetically targeted for the superoxide-forming vascular NADPH oxidase subunit, NOX1, have a blunted hypertensive response to Ang II. We therefore hypothesised that NOX1 is mechanistically involved in Ang II-induced superoxide production by cerebral arteries, and potentially in stroke outcome. Superoxide production by cerebral arteries and brains from wild-type (WT) and NOX1 deficient (NOX1-KO) mice was measured using L-012-enhanced chemiluminescence. Ischemic stroke was induced by middle cerebral artery occlusion (MCAO; 0.5 h). Cerebral blood flow was measured using transcranial laser-Doppler flowmetry. After 24 h, neurological assessment was performed, mice were euthanised, and infarct and edema volumes were calculated. Basal superoxide was similar between WT and NOX1-KO in brain and cerebral artery homogenates, and in intact cerebral arteries. However, Ang II-stimulated increases in superoxide were approximately 70% smaller in rings from NOX1-KO versus WT. During MCAO, rCBF decreased by approximately 75% in both WT and NOX1-KO, and increased to similar levels in each strain immediately following reperfusion. No difference in neurological score, total or subcortical cerebral infarct volume or edema volume was observed between WT and NOX1-KO mice. However, cortical infarct volume (which was very modest in WT) was approximately 4-fold greater in brains of NOX1-KO versus WT. Thus, NOX1 is essential for superoxide production in large cerebral arteries in response to Ang II but not under basal conditions. Furthermore, NOX1 does not appear to contribute to stroke size, and it may limit cortical infarct development following cerebral ischemia.
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PMID:Importance of NOX1 for angiotensin II-induced cerebrovascular superoxide production and cortical infarct volume following ischemic stroke. 1955 86

Hypertension is a major risk factor for the development of cardiovascular disease. Numerous placebo-controlled trials have demonstrated that treatment of hypertension results in substantial reduction of hypertension-related vascular events. The benefit of specific therapies beyond their effect on blood pressure is well established. Losartan is an orally-active, selective, nonpeptide, angiotensin II type 1-receptor antagonist (ARB), and it was the first in this class to be marketed. Several large-scale clinical trials have demonstrated that losartan and other ARBs have benefits in preventing cardiovascular disease. The Losartan Intervention For End point reduction in hypertension (LIFE) study demonstrated improved outcomes with losartan as compared with atenolol-based therapies in hypertensive patients with left ventricular hypertrophy, mainly because of stroke prevention. The Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated that losartan prevented the progression of diabetic nephropathy. In this review, evidence from these and other clinical trials with losartan shall be discussed. The pharmacodynamic and pharmacokinetic properties of losartan are described to explain its mechanisms of action. Among the ARB class, losartan possesses certain unique properties, which may enhance its cardiovascular protective effects. These include an increase of urinary uric acid excretion and antiatherothrombotic properties. Potential future roles for losartan and other ARBs shall be discussed, in addition to emphasizing areas in which evidence is currently lacking or indecisive, including head-to-head comparisons of ARBs and the effects of combining an ARB with angiotensin-converting-enzyme inhibitors.
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PMID:Losartan in cardiovascular disease. 1980 43

Excessive thyroid hormone induces cardiac hypertrophy and promotes heart failure in patients with hyperthyroidism, but the mechanism remains elusive. Rats were orally administered with levothyroxine (100 microg/kg, T(4)) for 4 weeks to induce hyperthyroidism. The calculated stroke volume decreased and the shortening amplitude-frequency relationship in unloaded contraction of isolated cardiomyocytes was negative in T(4)-treated rats. Apoptotic rates increased and DNA laddering was also detectable in T(4)-treated rat hearts. By contrast, in primary cultured cardiomyocytes, T(3) induced dose-dependent hypertrophy but did not affect the apoptotic rate. Angiotensin II further increased the apoptotic rate of T(3)-induced hypertrophied cardiomyocytes. The apoptotic rate was dependent on the extent of cardiomyocyte hypertrophy. These results suggest that cardiac contractility is enhanced during the early stage of hyperthyroidism, but decreased during the late stage of hyperthyroidism. The hypertrophied cardiomyocytes were also susceptible to apoptotic stimulation by angiotensin II. Depressed cardiac contractility and enhanced apoptosis may lead to heart failure in hypertrophied myocardium.
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PMID:Excessive thyroxine enhances susceptibility to apoptosis and decreases contractility of cardiomyocytes. 2012 86

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are indispensable therapeutic agents for treating hypertension and proteinuria in patients with diabetes mellitus. Studies have shown that the renin-angiotensin-aldosterone system (RAAS) has effects on various organ systems, including the central nervous system, heart, and kidneys. Angiotensin II has major deleterious effects on vascular compliance, vascular relaxation, and plasma markers of inflammation, which are surrogate markers of cardiovascular disease. Evidence is established from major trials that ACE inhibitors and ARB therapy improve these surrogate markers and reduce cardiovascular disease, renal disease, and stroke. Accumulating evidence also supports the newer class of medication, the direct renin inhibitor aliskiren, as beneficial in hypertensive persons with diabetes mellitus. In this article, we review the mechanisms through which inhibitors of the RAAS benefit persons with hypertension and decrease the development of cardiovascular and renal disease above and beyond blood pressure lowering.
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PMID:Pleiotropic effects of inhibitors of the RAAS in the diabetic population: above and beyond blood pressure lowering. 2042 64

Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective, reducing the incidence of stroke, improving cognition and decreasing the progression of Alzheimer's disease. Blockade of AT(1) receptors offers a novel and safe therapeutic approach for the treatment of illnesses of increasing prevalence and socioeconomic impact, such as mood disorders and neurodegenerative diseases of the brain.
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PMID:Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. 2103 50

Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII (two week) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient (Rag-1(-/-) ) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES(-/-) and P-selectin(-/-) mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII.
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PMID:Mechanisms underlying the cerebral microvascular responses to angiotensin II-induced hypertension. 2104 18

Angiotensin II type 1 receptor antagonists [ARBs (angiotensin receptor blockers)] are indicated for BP (blood pressure)-lowering, renal protection and cardioprotection in patients unable to tolerate ACEIs (angiotensin-converting enzyme inhibitors). A recent meta-analysis revealed an association between ARBs and tumour development, possibly due to enhancement of angiogenesis. However, published evidence is conflicting on the effects of ARBs on angiogenesis or the expansion of the existing vascular network. ARBs have been shown to exert primarily anti-angiogenic effects in basic science studies of cancer, retinopathy, peripheral artery disease and some models of cardiovascular disease. In animal and cellular models of myocardial infarction and stroke, however, ARB administration has been associated with robust increases in vascular density and improved recovery. The aim of the present review is to examine the angiogenic effects of ARBs in animal and cellular models of relevant disease states, including proposed molecular mechanisms of action of ARBs and the clinical consequences of ARB use.
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PMID:Angiotensin receptor blockers and angiogenesis: clinical and experimental evidence. 2148 24

Angiotensin-converting enzyme (ACE) inhibitors are a relatively homogenous drug class widely used today. They have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, chronic renal insufficiency, diabetes mellitus, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are partially attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction, altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include lower incidence of fatal and nonfatal myocardial infarction, reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications.
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PMID:[Angiotensin-converting enzyme inhibitors. Current indications]. 2149 92


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