Angiotensin type 1 receptor blockage improves ischemic injury following transient focal cerebral ischemia

Hosomi, Naohisa; Nishiyama, Akira; Ban, Camelia R; Naya, Takayuki; Takahashi, Tsutomu; Kohno, Masakazu; Koziol, James A.

doi:10.1016/j.neuroscience.2005.03.054

Cited by 67 publications

(58 citation statements)

References 24 publications

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“…Several clinical and experimental studies point toward important roles for the angiotensin system in the pathophysiology of ischemic stroke. Infusion of angiotensin II impairs a favorable outcome after cerebral ischemia (Hosomi et al, 1999), and blockade of angiotensin AT 1 receptors in the acute experimental ischemic stroke is beneficial (Engelhorn et al, 2004;Hosomi et al, 2005). Clinically, favorable effects of AT 1 receptor blockade in acute ischemic stroke were observed in the Acute Candesartan Cilexetil in Stroke Survivors (ACCESS) study, which showed that treatment with an AT 1 receptor blocker during 7 days after the onset of ischemic stroke improved cardiovascular morbidity and mortality during the following 12 months (Schrader et al, 2003).…”

Section: Ischemic Strokementioning

confidence: 99%

Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.

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Section: Ischemic Strokementioning

confidence: 99%

Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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“…58 -60 Effects of AT1 receptor blockers on brain AT1 receptors were suggested to mediate these neuroprotective characteristics. 58,61 The ability of different AT1 receptor blockers to cross the blood-brain barrier is controversial, however. 62,63 Candesartan was shown to enhance the TrkB receptor of brain-derived neurotrophic factor (BDNF), a neurotrophin well known for its neuroprotective effects.…”

Section: Antihypertensive Drugsmentioning

confidence: 99%

Multifunctional Actions of Approved and Candidate Stroke Drugs

Minnerup

Schäbitz

2009

Neurotherapeutics

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Summary: Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials have demonstrated that drugs targeting one or only a few of these pathways fail to improve clinical outcome after stroke. Drugs with multimodal actions have been suggested to overcome this challenge. In this review, we describe the mechanisms of action of agents approved for secondary prevention of ischemic stroke, such as antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit considerable properties beyond their classical mechanisms, including neuroprotective and neuroregenerative properties. In addition, candidate stroke drugs currently studied in clinical phase III trials are described. Among these, albumin, hematopoietic growth factors, and citicoline have been identified as promising agents with multiple mechanisms. These drugs offer hope that additional treatment options for the acute phase after a stroke will become available in the near future.

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“…9,12 Even in plasma, Ang II content (around 150 pM¼ 150 fmol ml À1 ) in those rats is also around 1/600 of the in vitro condition used in this study. 12 Therefore, we believe it is not easy to be similar Ang II stimulation conditions under in vivo cerebral ischemia to in vitro Ang II stimulation made in this study.…”

Section: Discussionmentioning

confidence: 76%

“…21,22 After stimulation, protein or mRNA was extracted as described previously. 9,23 The protein concentration was determined using the Bradford assay kit (Bio-Rad Laboratories, Hercules, CA, USA).…”

Section: Cell Culturementioning

confidence: 99%

“…[8][9][10] Additionally, brain Ang II is upregulated both in cerebral ischemia and Alzheimer's disease and can be regulated with systemic angiotensin type 1 (AT1) receptor blocker (ARB) treatment. 9,11,12 Thus, Ang II-induced astrocyte senescence may be involved in the pathology of cerebral ischemic injury and age-associated neurodegenerative disease.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II induces human astrocyte senescence through reactive oxygen species production

et al. 2011

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Angiotensin II (Ang II)-induced astrocyte senescence may be involved in cerebral ischemic injury and age-associated neurodegenerative disease. This study was conducted to determine the roles of reactive oxygen species production in Ang II-induced cellular senescence in cultured human astrocytes. Human astrocytes were stimulated with Ang II either with or without an angiotensin type 1 receptor blocker, CV11974, or an antioxidant, tempol. Application of Ang II to human astrocytes resulted in a concentration-dependent increase in staining for dihydroethidium. Ang II (100 nM for 30 min) increased the translocation of two cytosolic components of NADPH oxidase, p47phox and p67phox, to the cell membrane and formation of the complex of p47phox, p67phox and p22phox. Ang II concentration-dependently induced an increase in b-galactosidase staining. Pretreatment with CV11974 (100 nM) or tempol (3 mM) abolished Ang II-induced astrocyte b-galactosidase staining. Moreover, Ang II significantly upregulated p16 mRNA expression, which was inhibited by pretreatment with CV11974 or tempol. These findings indicate that superoxide production contributes to Ang II-induced astrocyte senescence.

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Angiotensin type 1 receptor blockage improves ischemic injury following transient focal cerebral ischemia

Cited by 67 publications

References 24 publications

Vascular plasticity in cerebrovascular disorders

Vascular plasticity in cerebrovascular disorders

Multifunctional Actions of Approved and Candidate Stroke Drugs

Angiotensin II induces human astrocyte senescence through reactive oxygen species production

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