Ang Ⅱ对成年大鼠心肌成纤维细胞分泌ET-1、NO功能的影响

目的：探讨血管紧张素Ⅱ（Ang Ⅱ）对成年大鼠心肌成纤维细胞（MFs）分泌内皮素-1（ET-1）、一氧化氮（NO）的影响。方法：采用酶消化法和差速贴壁分离法获取MFs，应用放射免疫分析法、硝酸还原酶法分别测定不同条件下培养的第二代心肌MFs培养液中的ET-1、NO水平。结果：一定浓度范围内的Ang Ⅱ可按剂量依赖方式促MFs分泌ET-1, 血管紧张素Ⅱ1型受体（AT₁R）拮抗剂losartan可阻断Ang Ⅱ的上述作用；Ang Ⅱ可抑制心肌MFs分泌NO，加losartan后再加Ang Ⅱ培养发现，MFs分泌NO能力不但不降低，而且还高于对照组（P<0.01）。结论：Ang Ⅱ可通过AT₁R促成年大鼠心肌MFs分泌ET-1，主要通过AT₁R影响MFs分泌NO，从而改变ET-1/NO比值。Ang Ⅱ可能通过影响MFs分泌的生物活性物质网络平衡关系改变，发挥其促心肌肥厚及心力衰竭效应。

Effects of AngⅡ on the production of ET-1, NO from adult rat myocardial fibroblasts

AIM: To investigate the effects of Ang Ⅱon the production of ET-1, NO from myocardial fibroblasts (MFs) of adult rat. METHODS: MFs were extracted by enzymatic digestion and anchorage velocity-dependent separation method. In this study, the changes of ET-1 and NO production from MFs in the second passage were examined by radioimmunoassay and by nitrate reductase-dependent assay, separatively. RESULTS: In a specific concentration range, AngⅡ increased ET-1 synthesis in MFs in a concentration-dependent manner. Losartan, the antagonist of angiotensin Ⅱ 1 type recepters (AT₁R), blocked the above effects. Ang Ⅱ may inhibit NO synthesis in MFs. When MFs were treated with losartan+Ang Ⅱ, the production of NO increased significantly, and was higher than that treated with the others (P<0.01). CONCLUSION: Ang Ⅱ may increase the production of ET-1 in MFs via AT₁R and affect NO production in MFs mainly via AT₁R to change the ratio of ET-1 and NO. Ang Ⅱ maybe exert inductive effects on myocardial hypertrophy and heart failure by affecting these complicated balances between bioactive factors produced from MFs.