肾性高血压大鼠延髓尾端神经元型一氧化氮合酶表达的改变

The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip Goldblatt hypertension rat

实验采用免疫组织化学方法观察两肾一夹肾性高血压大鼠延髓尾端两个区域 (延髓腹面降压区和尾端加压区 )内神经元型一氧化氮合酶 (neuronalnitricoxidesynthase,nNOS)表达的变化。肾性高血压大鼠延髓尾端这两个区域的nNOS的表达均增加 ,说明高血压时L Arg NO通路活性增强。NO的前体L Arg能增强nNOS的表达 ,nNOS抑制剂L NAME则降低nNOS的表达。以上两个区域nNOS表达变化的特点在肾性高血压 4周和 7周的动物相同 ,肾性高血压 7周的nNOS表达和 4周比较 。

Experiments were performed in male Sprague Dawley rats (150～200 g). A silver clip (0 2 mm internal diameter) was placed on the left renal artery of rats. After operation the rats were divided into 4 groups: sham group, 2K1C (two kidney one clip) group, 2K1C+Arg (2K1C and L Arg 150 mg/kg·d -1 by drinking) group, and 2K1C+NAME (2K1C and L NAME 10 mg/kg·d -1 i p ) group. The animals were studied at two time points (4 and 7 weeks after operation) corresponding to phases Ⅰ and Ⅱ of Goldblatt hypertension. The animals were deeply anesthetized with pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was removed, then placed in 25% sucrose in PB for 12 h in a 4℃ fridge. The 40 μm coronal slices of brainstems were cut with cryostat, collected in PBS for nNOS study by immunohistochemistry. The results showed that: (1) only a few neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal medulla, including the depressor area of the ventral surface of medulla oblongata (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number of nNOS positive neurons in caudal medulla was significantly increased in 2K1C Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive neurons in VSMd and CPA were 2K1C+Arg>2K1C>2K1C +NAME> sham. (3) L Arg enhanced the expression of nNOS whereas L NAME inhibited the expression of nNOS in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt hypertension rats at 4 weeks with that of the rats at 7 weeks.