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Chronic systemic treatment with blockers of angiotensin II type-1(AT1) receptors inhibits ischemia-induced apoptosis and reduces ischemic neuronal damage.However,the molecular mechanisms of AT1 receptor blockers in modulating neuronal apoptosis remain poorly understood.Pretreatment with irbesartan significantly suppressed cell apoptosis at 1-7 days following cerebral ischemia/reperfusion,increased levels of brain-derived neurotrophic factor,and elevated the ratios of Bcl-2/Bax and phosphorylated cyclic adenosine monophosphate response element-binding protein(pCREB)/CREB in the ischemic cortex at 1 day after reperfusion,as well as suppressing caspase-3 activation.Cerebral ischemia increased the mRNA expression of AT1 and AT2 receptors in the ischemic cortex,whereas irbesartan blocked this increase in AT1 expression but potentiated the expression of AT2.Therefore,this AT1 receptor blocker was neuroprotective by increasing the ratios of Bcl-2/Bax and pCREB/CREB,increasing brain-derived neurotrophic factor levels,inhibiting caspase-3 activation,and modulating AT receptor expression.
Chronic systemic treatment with blockers of angiotensin II type-1 (AT1) receptors inhibits ischemia-induced apoptosis and reduces ischemic neuronal damage. However, the molecular mechanisms of AT1 receptor blockers in modulating neuronal apoptosis remain poorly understood. Pleating with irbesartan significantly suppressed cell apoptosis at 1-7 days following cerebral ischemia / reperfusion, increased levels of brain-derived neurotrophic factor, and elevated the ratios of Bcl-2 / Bax and phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB) / CREB in the ischemic cortex at 1 day after reperfusion, as well as suppressing caspase-3 activation. Cerebral ischemia increased the mRNA expression of AT1 and AT2 receptors in the ischemic cortex, but irbesartan blocked this increase in AT1 expression but potentiated the expression of AT2.Therefore, this AT1 receptor blocker was neuroprotective by increasing the ratios of Bcl-2 / Bax and pCREB / CREB, increasing brain-derived ne urotrophic factor levels, inhibiting caspase-3 activation, and modulating AT receptor expression.