Mechanism of endothelial dysfunction in the acute brain ischemia and development of therapeutic intervention.

内皮型一氧化氮合酶（eNOS）是维持内皮功能的关键分子之一。脑缺血后小血管eNOS表达增加，但eNOS分子Ser1177磷酸化水平明显降低，提示eNOS功能障碍。Rho激酶抑制剂可通过增加eNOS磷酸化而减轻缺血损伤。高血压还可降低脑小血管eNOS磷酸化水平，加重缺血性损伤，降压治疗可保护eNOS磷酸化水平。磷酸二酯酶3能保护eNOS的磷酸化和功能，减轻脑缺血损伤。这些结果可能有助于开发新的治疗急性脑缺血和脑小血管病的方法。

Endothelial nitric oxide synthase(eNOS) is one of key molecules to maintain endothelial function. Although eNOS expression was increased in the brain small vessels after cerebral ischemia, phosphorylation level of Ser1177 of eNOS molecule was significantly reduced, indicating eNOS dysfunction. Rho-kinase inhibitor can ameliorate ischemic injury via increasing eNOS phosphorylation. Hypertension also decreased eNOS phosphorylation in the brain small vessels and deteriorated ischemic injury, and anti-hypertensive therapy could preserve eNOS phosphorylation. Additionally, phosphodiesterase3 could preserve eNOS phosphoryaltion and function and ameliorated cerebral ischemic injury. These results may contribute to develop new therapy for acute brain ischemia and brain small vessel disease.