Angiotensin Ⅱ Protects Cortical Neuron Injury Induced By Oxygen-glucose Deprivation And Its Mechaninsms

Objectives Brain ischemia or stoke, one of the leading causes of death and long-term disability in aged populations, often results in irreversible brain damage and subsequent loss of neuronal function. Hypoxia or ischemia can be characterized with a reduction in ATP as well as loss of ionic homeostasis resulting in plasma membrane depolarization, cellular stress, and glutamate release. The duration and severity of the hypoxic insult can result in apoptosis, and under the most severe conditions necrosis. While angiotensin II is best known for its role in blood pressure regulation, fluid balance, and neuroendocrine function, recent studies have shown that it also influences cell growth in several tissue types. These effects appear to be mediated through two receptor subtypes, the AT₁ and AT₂ receptors, which were initially characterized on the basis of their differential affinities for the angiotensin II non-peptide analogs, valsartan and PD123319, respectively . The AT₁ receptor has been shown to be primarily responsible for fluid and Na⁺ homeostasis, blood pressure and cardiovascular function. However, much less is known about the physiological roles of the AT2 receptor in both peripheral tissues and the central nervous system. Over the last decade, many studies have suggested that the AT₂ receptor may antagonize the actions of the AT₁ receptor . In addition, the AT₂ receptor has been suggested to participate in early development, cell proliferation and tissue repair. Makino et al. reported increases in AT₂ receptor mRNA levels following global brain ischemia in rats. Similar increases have...