Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats

Kagiyama, Tomoko; Kagiyama, Shuntaro; Phillips, M. Ian

doi:10.1016/s0167-0115(02)00223-9

Cited by 53 publications

(45 citation statements)

References 37 publications

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“…43 Studies of focal ischemia in genetically altered mice suggest that reductions in cerebral blood flow in the ischemic core and penumbra are in part mediated by Ang II. 44,45 Thus, endogenous Ang II appears to be a mediator of vascular dysfunction under some pathophysiological conditions. Unfortunately, relatively little is known regarding levels of Ang II in CSF, and, more importantly, within tissue and vessels, under normal conditions or in pathological states.…”

Section: Functional Implicationsmentioning

confidence: 99%

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

Didion

Faraci

2003

Stroke

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Background and Purpose-Angiotensin II (Ang II) produces oxidative stress in vascular cells in culture and in extracranial conduit arteries. The goal of this study was to examine the hypothesis that Ang II produces superoxide-mediated impairment of endothelial function in cerebral microvessels. Methods-Diameter of cerebral arterioles (baseline diameterϭ104Ϯ3 m) was measured with the use of a closed cranial window in anesthetized rabbits. Topical application of Ang II was used to avoid effects on arterial pressure. Results-Ang II (0.1 to 1 mol/L for 2 hours) had no effect on baseline diameter (change in diameter of Ϫ3Ϯ2% in response to 1 mol/L Ang II) but produced concentration-dependent inhibition of vasodilatation to the endotheliumdependent agonist bradykinin. For example, 1 mol/L Ang II inhibited responses to 1 nmol/L bradykinin by almost 80%. These inhibitory effects of Ang II were prevented by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron; 10 mmol/L) or diphenylene iodonium (DPI; 3 mol/L), an inhibitor of NAD(P)H oxidase. Ang II did not inhibit vasodilatation in response to nitroprusside, an endothelium-independent vasodilator. Conclusions-These findings are the first evidence that local Ang II produces superoxide-mediated vascular dysfunction in cerebral microvessels. The results with DPI suggest that the source of superoxide may be an NAD(P)H oxidase. Key Words: bradykinin Ⅲ cerebral circulation Ⅲ endothelium Ⅲ reactive oxygen species Ⅲ rabbits I n recent years, there has been renewed interest in the role of angiotensin II (Ang II) in vascular disease. In studies of extracranial blood vessels and vascular cells in culture, Ang II has been implicated as a major cause of oxidative stress, inflammation, and endothelial dysfunction as well as vascular hypertrophy and remodeling. [1][2][3][4] For example, Ang II increases superoxide formation in cultured vascular muscle and endothelium and within the wall of intact vessels. [5][6][7][8] We have found that superoxide is increased within the vessel wall and that endothelial dysfunction is present in animals made hypertensive using osmotic mini-pumps and in transgenic mice made hypertensive by expression of human renin and human angiotensinogen. 9,10 Vasomotor effects of Ang II have been studied in the cerebral circulation, but the results of these studies have been quite divergent. For example, acute administration of Ang II has been reported to produce constriction, [11][12][13][14][15][16][17] to have no effect, 18 or to produce dilation 19 -21 on cerebral blood vessels. In contrast to these studies, nothing is known regarding the possibility that Ang II produces oxidative stress or impairment of endothelium-dependent relaxation in the cerebral circulation. Thus, the goals of the present study were to (1) examine the hypothesis that Ang II produces endothelial dysfunction in the cerebral circulation and (2) determine whether endothelial dysfunction in response to Ang II was mediated by superoxide. The approach used involved applicatio...

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Section: Functional Implicationsmentioning

confidence: 99%

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

Didion

Faraci

2003

Stroke

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“…Ang II is a potent growth factor, which is known to stimulate endothelial cell proliferation (Otani et al, 1998), pericyte migration (Nadal et al, 2002), and hypertrophy of vascular smooth muscle (Perio et al, 1998). In the brain, Ang II promotes astrocyte proliferation (Sumners et al, 1994) and is upregulated in ischaemia (Kagiyama et al, 2003). Pharmacological blockade of the angiotensin converting enzyme (ACE), necessary for the liberation of Ang II, reduces diabetic neuropathy (Bui et al, 2003) and the progression of human diabetic patients to vasoproliferative retinopathy (Chaturvedi et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

AT₁ receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy

Downie

Pianta

Vingrys

et al. 2008

Glia

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We investigated the effect of receptor blockade induced by an angiotensin II type-1 receptor antagonist (AT(1)-RB) on glial and vascular changes in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity (ROP). OIR was induced in Sprague-Dawley rats by exposure to 80% oxygen from postnatal (P) days 0-11, followed by 7 days in room air. Control animals were in room air for the entire duration. One cohort of OIR and control pups received the AT(1)-RB valsartan (40 mg/kg/day intraperitoneal) from P11 to P18. The vascular response was examined immunocytochemically using retinal wholemounts and vertical sections labeled with endothelial (Isolectin-B4) and pericyte (NG2, desmin) markers. Glial cell changes were assessed by measuring cell numbers and immunoreactivity (S100beta, connexin-26, and glial fibrillary acidic protein). OIR resulted in extensive intravitreal neovascularization and under-development of the outer vascular plexus. Pericyte numbers were not significantly affected in OIR, although pericyte-endothelial (desmin-IB4) interactions were impaired. Peripheral astrocyte degeneration occurred between P11 and P13 with prominent Müller cell reactivity at P18. Valsartan imparted a protective effect on glia and blood vessels in OIR. At P18, valsartan-treated OIR retinae showed significantly greater astrocyte survival, improved revascularization of the retina, and reduced preretinal neovascularization and Müller cell reactivity. This study identifies a glio-vascular protective effect with AT(1)-RB in OIR.

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“…After MCAO in rats, levels of angiotensin II type 2 (AT2) and AT1 receptors in the brain significantly increase and decrease, respectively (28). Angiotensin II might further stimulate AT2 receptors in the presence of administered ARBs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Matrix Metalloproteinase-9 Activity by Trandolapril after Middle Cerebral Artery Occlusion in Rats

et al. 2007

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We investigated whether an angiotensin-converting enzyme (ACE) inhibitor could inhibit matrix metalloproteinase (MMP) activities in cerebral infarct lesions after middle cerebral artery occlusion (MCAO) in rats.After placebo or trandolapril (5 mg/kg per day) was administered orally for 7 days, we permanently occluded the right middle cerebral artery. ACE activity in extracts from the infarct side of placebo-treated rats was significantly higher than that in extracts from the non-infarct side from 5 days after MCAO, though they did not differ at 1 day. ACE activities in extracts from both hemispheric segments in the trandolapril-treated group were significantly decreased compared with those in the placebo-treated group before MCAO, and this significant reduction persisted even at 7 days after MCAO. In the placebo-treated group, MMP-9 and MMP-2 activities in the infarct side were significantly increased at 12 h and at 1 day after MCAO, respectively. Trandolapril treatment significantly reduced MMP-9 and MMP-2 activities to 68.5% and 53.2%, respectively. Seven days after MCAO, the ratios of infarct areas to the hemispheric sectional areas in placebo-and trandolapril-treated rats were 55.4 ± 2.1% and 30.9 ± 2.9%, respectively, and this difference was significant.Neurological severity scores were significantly improved from 1 to 7 days after MCAO in trandolapril-treated rats. Cumulative survival in trandolapril-treated rats was significantly increased compared with that in placebo-treated rats. Thus, the inhibition of MMP-9 by trandolapril might be part of the mechanism that prevents cerebral damage after cerebral ischemia. (Hypertens Res 2007; 30: [469][470][471][472][473][474][475]

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Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats

Cited by 53 publications

References 37 publications

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

AT₁ receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy

Inhibition of Matrix Metalloproteinase-9 Activity by Trandolapril after Middle Cerebral Artery Occlusion in Rats

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Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats

Cited by 53 publications

References 37 publications

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy

Inhibition of Matrix Metalloproteinase-9 Activity by Trandolapril after Middle Cerebral Artery Occlusion in Rats

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AT₁ receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy