左旋硝基精氨酸诱导的大鼠高血压主动脉粘着斑激酶活性改变

The changes of aortic focal adhesion kinase in hypertensive rats induced by N ω Nitro L Arginine

目的：探讨左旋硝基精氨酸（ＮωＮｉｔｒｏＬＡｒｇｉｎｉｎｅ， ＬＮＮＡ） 诱导的高血压大鼠血管中粘着斑激酶（ｆｏｃａｌａｄｈｅｓｉｏｎ ｋｉｎａｓｅ，ＦＡＫ）活性的变化，以及Ｅｎａｌａｐｒｉｌ 和Ｌｏｓａｒｔａｎ 对它的影响。方法：对Ｗｉｓｔａｒ 大鼠给予ＬＮＮＡ１５ ｍｇ·ｋｇ－ １·ｄ－ １ 腹腔注射，分别采用血管紧张素转换酶抑制剂Ｅｎａｌａｐｒｉｌ 和血管紧张素Ⅰ型受体拮抗剂Ｌｏｓａｒｔａｎ １０ ｍｇ·ｋｇ－１·ｄ－１ 灌胃，在第５ 周末，利用蛋白印迹杂交技术，检测主动脉中ＦＡＫ 的表达与活性。结果：ＬＮＮＡ 可明显诱导大鼠血压升高，在第５ 周末，与对照组相比血压平均升高４９％ （ Ｐ＜０ ．０１） ，Ｅｎａｌａｐｒｉｌ 和Ｌｏｓａｒｔａｎ 均可起到降压作用，在高血压组，ＦＡＫ 的表达和活力增高４０％ 和４２６ ％ ，Ｅｎａｌａｐｒｉｌ 和Ｌｏｓａｒｔａｎ 可抑制ＦＡＫ 的表达，降低ＦＡＫ 的活性。结论：在ＬＮＮＡ诱导高血压大鼠主动脉中，ＦＡＫ 活性增高，可能与血管重塑有关；血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂逆转血管重塑的作用可能是通过抑制ＦＡＫ 的功能实现的。

Objective: To investigate the expression and activity of vascular focal adhesion kinase (FAK) in hypertensive rats induced by N ω Nitro L Arginine ( L NNA). Methods: Experiments which were carried out on 24 male Wistar rats were randomly divided into four groups: L NNA group: treated with L NNA 15 mg·kg -1 ·d -1 by intraperitoneal injection for 5 weeks; Enalapril group: used L NNA as L NNA group, and treated with Enalapril 10 mg·kg -1 ·d -1 from the second week to the fifth week by gavage; Losartan group: treated with L NNA and Losartan 10 mg·kg -1 ·d -1 like previous group; Control group: used normal saline and tap water instead of L NNA, Enalapril and Losartan. At the end of the fifth week, the tail arterial pressures were measured with the RBP 1 pressure measurement. After that, the rats were killed and the aortae were taken out. And then, the Western Blot method was used to detect the expression and activity of FAK. Results: After having been used the L NNA for five weeks, the mean blood pressure of L NNA group increased 49% more than that of the control group. Enalapril and Losartan could reduce the pressure significantly. FAK expression and activity were detected in all aortae, and particularly abundant in L NNA group. Enalapril and Losartan were able to decrease the FAK expression and activity. Conclusion: In the aortae of hypertensive rats induced by L NNA, the FAK expression and activity increased, whereas Enalapril and Losartan could reduce it. The FAK may play an important role in the pathogenesis of vascular remodeling, and the effect of angiotensin converting enzyme inhibitors and the angiotensin Ⅱ receptor antagonist on the reverse remodeling may be related to their ability to reduce FAK activity.