Is the angiotensin ii type 2 receptor cerebroprotective?

Fournier, A; Achard, Jean Michel; Boutitie, Florent; Mazouz, Hakim; Mansour, Janette; Oprisiu, Roxana; Fernandez, Leonardo A.; Messerli, Franz H.

doi:10.1007/s11906-004-0067-8

Cited by 26 publications

(22 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because H 2 S causes vasodilation and vasodilators are generally cerebroprotective, leading to reduced infarct size; 23 this possible mechanism is much less likely.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Is a Mediator of Cerebral Ischemic Damage

Chen

Halliwell

et al. 2006

Stroke

251

191

View full text Add to dashboard Cite

Background and Purpose-We observed recently that elevated plasma cysteine levels are associated with poor clinical outcome in acute stroke patients. In a rat stroke model, cysteine administration increased the infarct volume apparently via its conversion to hydrogen sulfide (H 2 S). We therefore investigated the effects of H 2 S and the inhibition of its formation on stroke. Methods-Cerebral ischemia was studied in a rat stroke model created by permanent occlusion of the middle cerebral artery (MCAO). The resultant infarct volume was measured 24 hours after occlusion. Results-Administration of sodium hydrosulfide (NaHS, an H 2 S donor) significantly increased the infarct volume after MCAO. The NaHS-induced increase in infarct volume was abolished by the administration of dizolcilpine maleate (an N-methyl-D-aspartate receptor channel blocker). MCAO caused an increase in H 2 S level in the lesioned cortex as well as an increase in the H 2 S synthesizing activity. Administration of 4 different inhibitors of H 2 S synthesis reduced MCAO-induced infarct volume dose dependently. The potency of these inhibitors in effecting neuroprotection in vivo appeared to parallel their potency as inhibitors of H 2 S synthesis in vitro. It also appeared that most of the H 2 S synthesizing activity in the cortex results from the action of cystathionine ␤-synthase. Conclusions-The present results strongly suggest that H 2 S plays a part in cerebral ischemic damage after stroke.Inhibition of H 2 S synthesis should be investigated for its potential as a novel neuroprotective stroke therapy.

show abstract

“…However, because H 2 S causes vasodilation and vasodilators are generally cerebroprotective, leading to reduced infarct size; 23 this possible mechanism is much less likely.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Is a Mediator of Cerebral Ischemic Damage

Chen

Halliwell

et al. 2006

Stroke

251

191

View full text Add to dashboard Cite

show abstract

“…While the AT 1 receptor is distributed ubiquitously in the vasculature, kidney, adrenal gland, heart, liver and brain [25], the AT 2 receptor is only expressed in the adrenal medulla, uterus, ovary, vascular endothelium and distinct brain areas of adults [26]. The AT 2 receptor is upregulated in pathophysiologic conditions such as cardiac failure, myocardial infarct, cerebral ischemia, and skin and nervous system lesions [27,28,29,30]. …”

Section: Overview Of the Renin-angiotensin Systemmentioning

confidence: 99%

“…Third, ARBs preferentially block the AT 1 receptor and leave the AT 2 receptor unopposed. This is particularly relevant in stroke patients, since the AT 2 receptor is overexpressed in cerebral ischemia and AT 2 activation can lead to increased neuronal resistance to ischemia and enhanced collateral circulation recruitment [30]. Selective blockers of AT 1 have generally proven to be safe and effective in the treatment of both hypertension and cardiovascular disease.…”

Section: Overview Of the Renin-angiotensin Systemmentioning

confidence: 99%

Partial Peroxisome Proliferator-Activated Receptor Agonist Angiotensin Receptor Blockers

Towfighi

Ovbiagele

2008

Cerebrovasc Dis

View full text Add to dashboard Cite

Background and Purpose: Although their primary mechanism of action is blood pressure lowering, emerging data suggest that select angiotensin receptor blockers (ARBs), which partially activate the peroxisome proliferator-activated receptor γ (PPAR-γ), may effectively treat insulin resistance and dyslipidemia without the toxicity sometimes associated with full PPAR-γ agonists. Since up to 50% of the patients with ischemic stroke and transient ischemic attack harbor insulin resistance, drugs that simultaneously control hypertension and insulin resistance could be particularly useful for stroke prevention. Summary of Review: This review presents the experimental and preliminary clinical evidence supporting a promising role for partial PPAR-γ agonist ARBs in treating insulin resistance and the metabolic syndrome in patients with ischemic cerebrovascular disease. Conclusion: Partial PPAR-γ agonist ARBs by virtue of their multiple beneficial mechanisms of action could provide a single multipronged strategy for reducing future vascular events in persons with, or at risk for, stroke.

show abstract

“…The different actions on angiotensin receptors AT 1 and AT 2 in the renin-angiotensin-aldosterone system has been advocated as the hypothesis to explain the drug class differences in several stroke prevention studies despite a similar reduction in blood pressure [34]. The AT 1 receptor mediates several adverse effects of angiotensin II on blood pressure, cardiovascular remodeling and atherosclerosis.…”

Section: Arterial Hypertension and Risk Of Strokementioning

confidence: 99%

Action on Vascular Risk Factors: Importance of Blood Pressure and Lipid Lowering in Stroke Secondary Prevention

Fuentes

Ortega-Casarrubios²,

Martinez³

et al. 2007

Cerebrovasc Dis

View full text Add to dashboard Cite

Introduction: Secondary stroke prevention comprises a broad spectrum of therapeutic actions that includes the appropriate management of risk factors and the action on blood pressure and serum lipids that are of great importance to decrease stroke recurrences. Methods: We conducted a review of the published studies analyzing the relevance of the treatment of blood pressure and serum lipids, with special attention to recent findings of clinical trials and current guidelines on stroke secondary prevention. Results: The relationship between blood pressure and stroke has been widely demonstrated; however, the role of serum lipids has been discussed for a long time. Recent results from epidemiological studies and clinical trials have demonstrated its role as modifiable risk factor for stroke. Blood pressure and lipid lowering are associated with significant reductions in recurrent strokes as well as in other vascular events in transient ischemic attack (TIA) or stroke patients. The PROGRESS and MOSES trials suggest that diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers could confer additional benefits in stroke patients, and the SPARCL study did so for statins. These drugs are not only efficacious in the reduction of stroke recurrences, but also in other cardiovascular events. Conclusions: Blood pressure and serum lipids are two important and modifiable vascular risk factors that should be taken into consideration when planning secondary stroke prevention measures. This approach should include hypotensive drugs (mainly the combination of diuretics and ACE inhibitors) with the objective to maintain normal blood pressure, avoiding levels >130/80 mm Hg in all stroke patients, and statins (atorvastatin 80 mg) in patients with noncardioembolic TIA or stroke.

show abstract

Is the angiotensin ii type 2 receptor cerebroprotective?

Cited by 26 publications

References 56 publications

Hydrogen Sulfide Is a Mediator of Cerebral Ischemic Damage

Hydrogen Sulfide Is a Mediator of Cerebral Ischemic Damage

Partial Peroxisome Proliferator-Activated Receptor Agonist Angiotensin Receptor Blockers

Action on Vascular Risk Factors: Importance of Blood Pressure and Lipid Lowering in Stroke Secondary Prevention

Contact Info

Product

Resources

About