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

Angiotensin II (Ang II) type 2 (AT2) receptors are abundantly expressed not only in the fetal brain where they probably contribute to brain development, but also in pathological conditions to protect the brain against stroke; however, the detailed mechanisms are unclear. Here, we demonstrated that AT2 receptor signaling induced neural differentiation via an increase in MMS2, one of the ubiquitin-conjugating enzyme variants. The AT2 receptor, MMS2, Src homology 2 domain-containing protein-tyrosine phosphatase 1 (SHP-1), and newly cloned AT2 receptor-interacting protein (ATIP) were highly expressed in fetal rat neurons and declined after birth. Ang II induced MMS2 expression in a dose-dependent manner, reaching a peak after 4 h of stimulation, and this effect was enhanced with AT1 receptor blocker, valsartan, but inhibited by AT2 receptor blocker PD123319. Moreover, we observed that an AT2 receptor agonist, CGP42112A, alone enhanced MMS2 expression. Neurons treated with small interfering RNA of MMS2 failed to exhibit neurite outgrowth and synapse formation. Moreover, the increase in AT2 receptor-induced MMS2 mRNA expression was enhanced by overexpression of ATIP but inhibited by small interfering RNA of SHP-1 and overexpression of catalytically dominant-negative SHP-1 or a tyrosine phosphatase inhibitor, sodium orthovanadate. After AT2 receptor stimulation, ATIP and SHP-1 were translocated into the nucleus after formation of their complex. Furthermore, increased MMS2 expression mediates the inhibitor of DNA binding 1 proteolysis and promotes DNA repair. These results provide a new insight into the contribution of AT2 receptor stimulation to neural differentiation via transactivation of MMS2 expression involving the association of ATIP and SHP-1.
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PMID:Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1. 1706

Angiotensin II (Ang II) plays a pivotal role in cardiovascular remodeling leading to hypertension, myocardial infarction, and stroke. Pitavastatin, an HMG-CoA reductase inihibitor, is known to have pleiotropic actions against the development of cardiovascular remodeling. The objectives of this study were to clarify the beneficial effects as well as the mechanism of action of pitavastatin against Ang II-induced organ damage. C57BL6/J mice at 10 weeks of age were infused with Ang II for 2 weeks and were simultaneously administered pitavastatin or a vehicle. Pitavastatin treatment improved Ang II-induced left ventricular hypertrophy and diastolic dysfunction and attenuated enhancement of cardiac fibrosis, cardiomyocyte hypertrophy, coronary perivascular fibrosis, and medial thickening. Ang II-induced oxidative stress, cardiac TGFbeta-1 expression, and Smad 2/3 phosphorylation were all attenuated by pitavastatin treatment. Pitavastatin also reduced Ang II-induced cardiac remodeling and diastolic dysfunction in eNOS-/- mice as in wild-type mice. In eNOS-/- mice, the Ang II-induced cardiac oxidative stress and TGF-beta-Smad 2/3 signaling pathway were enhanced, and pitavastatin treatment attenuated the enhanced oxidative stress and the signaling pathway. Moreover, pitavastatin treatment reduced the high mortality rate and improved renal insufficiency in Ang II-treated eNOS-/- mice, with suppression of glomerular oxidative stress and TGF-beta-Smad 2/3 signaling pathway. In conclusion, pitavastatin exerts eNOS-independent protective actions against Ang II-induced cardiovascular remodeling and renal insufficiency through inhibition of the TGF-beta-Smad 2/3 signaling pathway by suppression of oxidative stress.
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PMID:Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency. 1796 81

Angiotensin II type-1 receptor blockers are widely used with the expectation of prevention of stroke, potential effects to ameliorate of type-2 diabetes, which seems to be closely associated with the impairment of cognitive function in humans. Recently, we have reported that an angiotensin II type-1 receptor blocker prevented cognitive impairment in mice after focal cerebral ischemia, at least partly through an angiotensin II type-2 receptor-mediated increase in a neuroprotective factor, methyl methanesulfonate sensitive-2. Here, we examined the possibility that an angiotensin II type-1 receptor blocker could improve cognitive function in a type-2 diabetic mouse model, KK-A(y). KK-A(y) mice subjected to 20 trials of a passive avoidance task every week from 8 weeks exhibited a significantly impaired avoidance rate, and moreover, its age-dependent decline, especially after 14 weeks of age, compared with age-matched C57BL6 mice. Oral administration of candesartan at a nonhypotensive dose (0.005% in laboratory chow) in KK-A(y) mice improved cognitive function and inhibited the impairment of cognitive decline. Methyl methanesulfonate sensitive-2 expression in the brain was lower in KK-A(y) mice than in C57BL6 mice. Treatment with candesartan markedly increased mRNA expression of angiotensin II type-2 receptor and methyl methanesulfonate sensitive-2 in the brain in KK-A(y) mice, determined by quantitative RT-PCR. In KK-A(y) mice treated with candesartan, age-dependent increases in blood glucose and insulin were significantly suppressed. Our results suggest that candesartan ameliorates the impaired cognitive function in type-2 diabetes mice, at least because of an increased expression of methyl methanesulfonate sensitive-2, a neuroprotective factor, in addition to improvement of glucose intolerance.
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PMID:Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. 1796

Moderate elevations in blood pressure translate to significant increases in cardiovascular and cerebro vascular risk. Beneficially, this relationship allows small decreases in blood pressure to be associated with risk reduction. Both the renin-angiotensin system and the sympathetic nervous system are involved in hypertension, hence targeting these systems is likely to be of benefit in the treatment of hypertension. Angiotensin II type 1 receptor blockers (ARBs) are used for controlling blood pressure and treating heart failure in a broad range of patients, including those with diabetes and the elderly. Not only have ARBs shown good efficacy and tolerability, they also appear to have a protective effect that goes beyond that expected from the reduction of blood pressure. The ARB eprosartan is a nonbiphenyl nontetrazole angiotensin II type 1 receptor (AT1) antagonist, which acts to decrease total peripheral resistance. Eprosartan acts at vascular AT1 receptors (postsynaptically) and at presynaptic AT1 receptors, where it inhibits noradrenaline release. In clinical studies, eprosartan has been shown to significantly reduce cardiovascular and cerebrovascular events, whilst avoiding the persistent cough that commonly occurs with the use of angiotensin-converting enzyme inhibitors. Eprosartan can also be differentiated from other ARBs due to its noradrenergic effects, which other ARBs used at therapeutic doses do not possess. Eprosartan, therefore, represents a useful therapeutic option in the management of patients with hypertension, including those with a history of stroke or with co-morbid type 2 diabetes mellitus.
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PMID:Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. 1809 7

Angiotensin (AT) II and noradrenaline play major roles in hypertension, stroke and coronary heart disease, which are themselves interlinked. Harmful effects of AT II are not blocked solely by angiotensin-converting enzyme inhibitors, as it is now evident that AT II is generated by other enzymes such as chymase. Angiotensin II also stimulates noradrenaline release modulated by presynaptic receptors on sympathetic nerves. Numerous studies have defined the action of the AT II type 1 receptor blocker (ARB) eprosartan as controlling noradrenergic and adrenergic effects, resulting from actions on the renin-angiotensin-aldosterone system and the sympathetic nervous system. Clinical studies have been carried out to assess the effects of ARBs on morbidity and mortality. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial compared the effects of valsartan and the calcium channel blocker (CCB) amlodipine in over 15,000 patients at high risk of a cardiac event. Results showed that blood pressure was reduced by both treatments and cardiac mortality/morbidity was similar in both groups. By contrast, the Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study (n = 1405) generated results which differed from the VALUE study, in that blood pressure was reduced by both eprosartan and nitrendipine, but eprosartan reduced all cardiovascular and cerebrovascular events to a greater extent than nitrendipine. It is also possible that any delayed clinical benefit of eprosartan could be due to reverse cardiac remodelling. Eprosartan, by blocking AT II receptors, reducing noradrenaline release and blocking catecholamine actions, may, therefore, provide greater protection against vascular events than CCBs or other ARBs.
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PMID:Risk reduction by preventing stroke: need for blockade of angiotensin II and catecholamines? 1809 11

Atrial fibrillation (AF) is an epidemic, affecting 1% to 1.5% of the population in the developed world. Projected data from the population-based studies suggest that the prevalence of AF will grow at least 3-fold by 2050. The health and economic burden imposed by AF and AF-related morbidity is enormous. Atrial fibrillation has a multiplicity of causes ranging from genetic to degenerative, but hypertension and heart failure are the commonest and epidemiologically most prevalent conditions associated with AF as both have been shown to create an arrhythmogenic substrate. Several theories emerged regarding the mechanism of AF, which can be combined into two groups: the single focus hypothesis and the multiple sources hypothesis. Several lines of evidence point to the relevance of both hypotheses to the mechanism of AF, probably with a different degree of involvement depending on the variety of AF (paroxysmal or persistent). Sustained AF alters electrophysiological and structural properties of the atrial myocardium such that the atria become more susceptible to the initiation and maintenance of the arrhythmia, a process known as atrial remodeling. Angiotensin II has been recognized as a key element in atrial remodeling in association with AF opening the possibility of exploitation of "upstream" therapies to prevent or delay atrial remodeling. The clinical significance of AF lies predominantly in a 5-fold increased risk of stroke. The limitations of warfarin prompted the development of new antithrombotic drugs, which include anticoagulants, such as direct oral thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). Novel mechanical approaches for the prevention of cardioembolic stroke have recently been evaluated: percutaneous left atrial appendage occluders, minimally invasive surgical isolation of the left atrial appendage, and implantation of carotid filtering devices.
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PMID:Update on atrial fibrillation: part I. 1825 25

A brain renin angiotensin system (RAS) and its role in cardiovascular control and fluid homeostasis was at first controversial. This was because a circulating kidney-derived renin angiotensin system was so similar and well established. But, the pursuit of brain RAS has proven to be correct. In the course of accepting brain RAS, high standards of proof attracted state of the art techniques in all the new developments of biology. Consequently, brain RAS is a robust concept that has enlightened neuroscience as well as cardiovascular physiology and is a model neuropeptide system. Molecular biology confirmed the components of brain RAS and their location in the brain. Transgenic mice and rats bearing renin and extra copies of angiotensinogen genes revealed the importance of brain RAS. Cre-lox delivery in vectors has enabled pinpoint gene deletion of brain RAS in discrete brain nuclei. The new concept of brain RAS includes ACE-2, Ang1-7, and prorenin and Mas receptors. Angiotensin II (ANG II) generated in the brain by brain renin has many neural effects. It activates behavioral effects by selective activation of ANG II receptor subtypes in different locations. It regulates sympathetic activity and baroreflexes and contributes to neurogenic hypertension. New findings implicate brain RAS in a much wider range of neural effects. We review brain RAS involvement in Alzheimer's disease, stroke memory, and learning alcoholism stress depression. There is growing evidence to consider developing treatment strategies for a variety of neurological disease states based on brain RAS.
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PMID:Brain renin angiotensin in disease. 1838 68

The present study examined the levels of Angiotensin II type 1 receptor (AT(1)) and type 2 receptor (AT(2)) in the brain stem and cerebral cortex of the stroke-prone spontaneously hypertensive rat (SHR-sp) after long-term treatment with three types of antihypertensive drugs: valsartan, enalapril, and amlodipine. In both tissues, expression of the AT(1) was decreased by administration of each drug. Expression of the AT(2) was decreased in the cerebral cortex by drug administration, but did not change in the brain stem. This study may contribute to elucidating the relationship between AT(1) and AT(2) expressions and the effect of antihypertensive drugs in SHR-sp brain.
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PMID:Decreased expression of angiotensin II type 1 and type 2 receptors in the brain after long-term administration of antihypertensive drugs in stroke-prone spontaneously hypertensive rat. 1840 96

The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study was performed to investigate the relationship between blood pressure (BP) and development of stroke or myocardial infarction (MI) in Japanese hypertensive patients. A total of 26,512 hypertensive patients (mean age: 62.2 years, 43.9% men) were analyzed. All patients received open-labelled losartan for a maximum of 5 years. Endpoints were stroke, MI including sudden cardiac death, and all cardiovascular (CV) events (stroke and MI). The mean observation period was 3.0 years. The mean baseline systolic/diastolic BP was 165.8/94.8 mmHg and decreased to 141.6/82.0 mmHg during treatment. The incidences of stroke, MI, and total CV events were 3.90, 1.02, and 4.92 per 1,000 patient-years, respectively. Aging, diabetes, a history of CV disease, and smoking were independent risk factors for CV events. The risk of all CV events was positively related to BP level during treatment, and increased significantly when the BP exceeded 140/90 mmHg. Age was a strong contributor to CV events, but about a half of the very elderly patients (>or=85 years, n=692) had a BP below 140/90 mmHg during treatment and significantly fewer events occurred in these patients than in those with a BP of 140/90 mmHg or higher. These results suggest that BP should be below 140/90 mmHg in Japanese patients with hypertension for reducing the risk of CV events. BP was controlled below 140/90 mmHg in a half of the very elderly hypertensive patients in this study, and these patients also had a lower incidence of CV events.
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PMID:Impact of blood pressure control on cardiovascular events in 26,512 Japanese hypertensive patients: the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study, a prospective nationwide observational study. 1849 66

White-coat hypertension (HT) and masked HT can be identified by home blood pressure (BP) measurement. The prevalence of these subtypes and the associated risk of cardiovascular disease have not been fully investigated among Japanese hypertensive patients. The risk of cardiovascular events due to HT and its relationship with home BP measurement were examined among Japanese hypertensive patients receiving treatment in the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study, a nationwide prospective observational study. Both home and clinic BP were measured during treatment, and the occurrence of cardiovascular events was monitored in 4,596 Japanese patients (mean age of 60.8 years, 43.2% men, and mean follow-up period of 3.5 years). HT was defined as a systolic BP > or =140 mmHg for clinic BP and > or =135 mmHg for home BP while on treatment. The relative risk of all cardiovascular events and stroke increased along with higher clinic and home BP levels during treatment. The prevalence of white-coat HT, masked HT, well-controlled HT, and poorly controlled HT was 12.6%, 19.5%, 23.8%, and 44.1%, respectively. The relative risk of cardiovascular events was not significantly increased in the poorly controlled HT (relative risk [RR]: 2.05, 95% confidence interval [CI]: 0.77-5.45), white-coat HT (RR: 0.77, 95% CI: 0.15-3.96), and masked HT (RR: 2.00, 95% CI: 0.67-5.98) subgroups compared with the well-controlled-HT subgroup; however, the risk of masked HT was similar to that of poorly controlled HT. Monitoring both clinic and home BP is important to diagnose masked HT and to prevent cardiovascular disease in this subtype of HT. However, further investigation is required to fully characterize the cardiovascular risks associated with masked HT among Japanese patients receiving treatment.
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PMID:The importance of home blood pressure measurement for preventing stroke and cardiovascular disease in hypertensive patients: a sub-analysis of the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study, a prospective nationwide observational study. 1901 98


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