高血压大鼠主动脉一氧化氮合成途径的变化  

Changes in Nitric Oxide Generation Pathway of the Aorta in Hypertensive Rats

作　　者：袁杰[1] 李菊香[1] 张宝红[1] 耿斌 刘玉雷 唐朝枢[1] 

机构地区：[1]北京大学第一医院心血管病研究所,北京100034

出　　处：《高血压杂志》2002年第5期463-467,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助 (编号 :39970 2 95 )

摘　　要：目的　观察高血压大鼠主动脉内膜、中膜和外膜一氧化氮合成途径的改变 ,并探讨其可能的病理生理意义。方法　Wistar大鼠缩窄腹主动脉复制高血压模型 ,动物随机分为对假手术组和高血压组。取大鼠主动脉 ,分离血管内膜、中膜和外膜。分别测定其亚硝酸盐 (NO2- )生成量、一氧化氮合酶 (NOS)活性及L -精氨酸 (L Arg)转运 ,免疫组化染色检测诱导型一氧化氮合酶 (iNOS)的分布。结果　与假手术组相比 ,高血压大鼠血浆中一氧化氮代谢产物 (NOx)高2 6 .2 % (P <0 0 5 ) ;主动脉NO2- 生成低 6 5 .8% (P <0 0 1) ,中膜及外膜孵育液的NO2- 生成量分别高 5 9.6 %和 12 3.6 % (均P <0 0 1) ;主动脉内膜NOS活性低 5 9.3% (P <0 0 1) ,中膜和外膜NOS活性分别高 6 2 .6 %和 118.7% (均P <0 0 1) ;血管内膜L Arg转运率低 6 2 .5 % (P <0 0 1) ,中膜和外膜L Arg转运率分别高 5 3.7%和 99.8% (均P <0 0 1)。iNOS免疫组化染色显示 ,高血压大鼠血管中膜和外膜尤其是外膜iNOS阳性染色明显增强。结论　高血压大鼠血管壁一氧化氮合成与代谢发生改变 ,血管内膜L Arg NOS NO途径受抑 ,而中膜和外膜尤其是外膜的L Arg NOS NO系统的活性增强 ,血管生成的NO增多。提示血管中膜和外膜源NO增多在高血压时可能具有一定的代偿作?Objective To observe the change in nitrite oxide (NO) generation system of the vascular adventitia, media and intima in hypertensive rat and investigate its possible pathophysiological mechanisms. Methods The hypertensive model was made in Wistar rat by abdominal aorta constriction. The rats were randomly divided into sham and hypertension groups. The intima, media and adventitia were separated from aorta. NO production (NO 2 -), nitric oxide synthase(NOS) activity and L arginine transport were measured separately. Inducible NOS (iNOS) distribution was detected by immunohistochemistry. Results Compared with sham group, in hypertensive rats, plasma levels of NO x (NO 2 - +NO 3 -) elevated by 15.6% ( P <0 05). The intima generated NO 2 - decreased by 65.8%( P <0 01), while media generated NO 2 - increased 59.6%( P <0 01), and the adventitia generated NO 2 - increased obviously by 123.6%( P <0 01). The NOS activity in the intima decreased by 59.3%( P <0 01), but it increased by 62.6% and 118.7% ( P <0 01) in the media layer and adventitia, respectively. The L arginine transport of the intima decreased by 62.5% ( P <0 01), However, it increased by 53.7% and 99.8% ( P <0 01) in the media layer and adventitia, respectively. The results of iNOS immunohistochemistry showed that there were obviously positive stain in the media layer and adventitia, especially the adventitia, compared with the control vessels. Conclusion The vascular synthesis and metabolism of NO in the hypertensive rats was in disorder. L arginine NOS NO pathway in the vascular intima was suppressed in hypertension however, this pathway in the aortic media layer and adventitia, especially the adventitia, was activated. NO production of the vessels in hypertensive rats was increased. These results suggest that an increase of NO production in the media and adventitia might play a compensatory effect during hypertensive processes.

关 键 词：高血压 大鼠 主动脉 一氧化氮合成途径 一氧化氮合酶 L-精氨酸转运 

分 类 号：R544.1[医药卫生—心血管疾病]