Angiotensin AT2 Receptor Stimulation Increases Survival in Gerbils with Abrupt Unilateral Carotid Ligation

Fernandez, Leonardo A.; Caride, Vicente J.; Strömberg, Christer; Näveri, Liisa; Wicke, J. D.

doi:10.1097/00005344-199424060-00011

Cited by 51 publications

(27 citation statements)

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“…Several animal studies have shown that treatment with angiotensin-II increasers either before or following induction of brain ischemia lead to improved survival [27, 28]. This supports the hypothesis that ARB confer neuroprotection by selectively blocking angiotensin-II type 1 receptors leading to an upregulation and unopposed stimulation of the type 2 receptors.…”

Section: Discussionsupporting

confidence: 52%

Pre-Stroke Use of Antihypertensives, Antiplatelets, or Statins and Early Ischemic Stroke Outcomes

Keezer

Zhu

et al. 2009

Cerebrovasc Dis

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Background: The effect of pre-stroke use of antihypertensives, antiplatelets, and statins on initial severity and early outcome of ischemic stroke is uncertain. Methods: We performed a retrospective chart review of 553 consecutive acute ischemic stroke patients presenting to the Montreal General Hospital between April 1st 2002 and October 15th 2005. We defined a severe stroke as a Canadian Neurological Scale score of ≤7 and a poor early outcome as a modified Rankin Scale score of >3 at 10 days post-stroke. Results: In total, 339 patients were included. Superior early functional outcome was associated with the premorbid use of statins (OR = 0.50, 95% CI: 0.25–1.00) and the combination of all 3 medications (OR = 0.37, 95% CI: 0.16–0.87). Angiotensin-II-decreasing agents were associated with an increased risk of severe strokes (OR = 2.13, 95% CI: 1.00–4.52). Conclusions: Pre-stroke use of statins and the combination of antihypertensives, antiplatelets, and statins were both associated with a favorable functional outcome at 10 days post-stroke. Angiotensin-II-decreasing agents were associated with increased initial stroke severity.

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Section: Discussionsupporting

confidence: 52%

Pre-Stroke Use of Antihypertensives, Antiplatelets, or Statins and Early Ischemic Stroke Outcomes

Keezer

Zhu

et al. 2009

Cerebrovasc Dis

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“…Several clinical and experimental studies presented earlier have provided evidence that AII can be cerebroprotective and its effects on ischaemic stroke are mediated through local stimulation of the AT 2 receptors. [36][37][38][39][40] 28,30,33 and especially in elderly patients with isolated systolic hypertension. 29,31 Other mechanisms by which ARBs could reduce the incidence of new or recurrent stroke include the beneficial effects of some ARBs on blood glucose control by increasing insulin sensitivity, 49,50 their platelet antiaggregating effects, [51][52][53][54] their hypouricemic effects 66,67 and their atrial antifibrillatory effects.…”

Section: Discussionmentioning

confidence: 99%

“…The authors postulated that the beneficial effects of AII on cerebral ischaemia were independent of blood pressure and possibly due to the enhancement of pre-existing collateral circulation and reduction of cerebral ischaemia. In studies performed later, Fernandez et al 38 showed that the protective effects of AII on the brain ischaemia of gerbils was mediated through stimulation of the AT 2 receptors. Brain ischaemic gerbils pretreated with either the selective AT 1 receptor blocker losartan, or the selective AT 2 receptor agonist PD-123319, had decreased mortality compared to gerbils pretreated with normal saline or the ACEI enalapril.…”

Section: Aii-mediated Effects Of Arbsmentioning

confidence: 99%

“…[36][37][38] Fernandez et al 36 showed that AII exerted a protective role against acute vascular ischaemia and transitory paralysis of the hind limbs of the rat by applying an aortic ligature between the kidneys, thus rendering the left kidney ischaemic and producing renovascular hypertension. Removal of the ischaemic kidney reduced the level of plasma rennin activity and blood pressure to within normal values, but the limb's ischaemia persisted for 24 h. Exogenous administration of AII increased the blood pressure and restored the limb ischaemia by increasing the blood flow to the muscles of the hind limb.…”

Section: Aii-mediated Effects Of Arbsmentioning

confidence: 99%

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Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence

Chrysant

2005

J Hum Hypertens

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Stroke is a major cause of death and disability and its incidence increases linearly with age and the level of systolic and diastolic blood pressure. Stroke, besides being a cause of long-term disability for the affected person, also imposes a significant burden on society and healthcare costs. Although good blood pressure control is very critical for stroke prevention, angiotensin receptor blockers (ARBs) may be superior to angiotensin-converting enzyme inhibitors (ACEIs) for the same degree of blood pressure control. This hypothesis has clinical and experimental support. ARBs prevent stroke incidence by blocking the angiotensin II (AII), AT 1 receptors preventing brain ischaemia and allowing AII to stimulate the unoccupied AT 2 receptors, which improve brain ischaemia. ACEIs, by reducing AII generation, are less effective in preventing stroke. This hypothesis provides evidence that AII plays an important role in the prevention of stroke. Certain ARBs like losartan, and telmisartan, irbesartan and candesartan possess additional properties which may play a role in stroke prevention, which is independent of AII. These include antiplatelet aggregating, hypouricemic, antidiabetic and atrial antifibrillatory effects. However, the most critical factor in stroke prevention is good blood pressure control irrespective of drug used.

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“…ATII promotes the proliferation of different cell types including astrocytes [9,10], and is upregulated together with its AT2-R after ischemic brain injury [11]. The data concerning the effects of ATII during ischemic damage are contradictory: Whilst exogenous application of ATII or AT2-R stimulation decreases the mortality rate in gerbils with unilateral carotid ligation [12,13], and the long term blockade of AT1-R in rat brain improves the neurological outcome and reduces the infarct volume after experimental ischemia [14], ATII also mediates programmed cell death through AT2-R in different cell types [15]. So far, the mechanisms of ATII action on the different CNS cell types and the involvement of its receptor subtypes in protective and pathophysiological mechanisms during hypoxia-associated injury of the brain are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin Receptor Type 1 Blockade in Astroglia Decreases Hypoxia-Induced Cell Damage and TNF Alpha Release

et al. 2007

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The present study investigated the role of angiotensin receptors (AT-R) in the survival and inflammatory response of astroglia upon hypoxic injury. Exposure of rat astroglial primary cultures (APC) to hypoxic conditions (HC) led to decreased viability of the cells and to a 3.5-fold increase in TNF-alpha release. AT-R type1 (AT1-R) antagonist losartan and its metabolite EXP3174 decrease the LDH release (by 36 +/- 9%; 45 +/- 6%) from APC under HC. Losartan diminished TNF-alpha release (by 40 +/- 15%) and the number of TUNEL-cells by 204 +/- 38% under HC, alone and together with angiotensin II (ATII), while EXP3174 was dependent on ATII for its effect on TNF-alpha. The AT2-R antagonist, PD123.319, did not influence the release of LDH and TNF-alpha under normoxic (NC) and HC. These data suggest that AT1-R may decrease the susceptibility of astrocytes to hypoxic injury and their propensity to release TNF-alpha. AT1-R antagonists may therefore be of therapeutic value during hypoxia-associated neurodegeneration.

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Angiotensin AT2 Receptor Stimulation Increases Survival in Gerbils with Abrupt Unilateral Carotid Ligation

Cited by 51 publications

References 0 publications

Pre-Stroke Use of Antihypertensives, Antiplatelets, or Statins and Early Ischemic Stroke Outcomes

Pre-Stroke Use of Antihypertensives, Antiplatelets, or Statins and Early Ischemic Stroke Outcomes

Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence

Angiotensin Receptor Type 1 Blockade in Astroglia Decreases Hypoxia-Induced Cell Damage and TNF Alpha Release

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