卡托普利治疗对SHR大鼠遗传血压、左心室肥厚及心肌胶原的影响

目的探讨卡托普利对自发性高血压大鼠（ＳＨＲ）的血压及左心室肥厚的影响。方法选用一组ＳＨＲ（Ｆ０），从交配之日起每天给卡托普利（２０ｍｇ／ｋｇ），其子代（Ｆ１）持续治疗到１６周时分为２组。第一组Ｆ１ａ在交配时继续用药治疗；第二组Ｆ１ｂ交配时停药。第二代两组小鼠（Ｆ２）出生后，Ｆ２ａ继续用药治疗到１６周停药；Ｆ２ｂ不用药治疗。分别观察其血压，左心室重量（ＬＶＭ），左心室重量与体重比（ＬＶＭ／ＢＷ）及测定左心室羟脯氨酸浓度和计算机图像分析心肌胶原的含量。结果发现在停药前动物血压处于较低的水平，但明显高于ＷＫＹ；而停药后血压明显回升到接近ＳＨＲ的水平。Ｆ２ａ表现基本一致；而Ｆ２ｂ的血压与对照组ＳＨＲ一样，明显高于Ｆ２ａ组。心肌内羟脯氨酸浓度及胶原含量，在Ｆ２ａ明显较ＳＨＲ和Ｆ２ｂ低，接近ＷＫＹ水平。结论卡托普利治疗并不能防止ＳＨＲ的高血压的遗传发展，但可以减低左心室肥厚。

卡托普利合成方法的改进

甲基丙烯酸与溴化氢反应得到３－溴－２－甲基丙酸，后者经用氯化亚砜氯化、与Ｌ－脯氨酸缩合得到缩合酸．缩合酸再经分拆、巯基化得到卡托普利．

The Releasing Effects of Captopril and Sodiun Nitroprusside on Endothelin-1 in Vascular Smooth Muscle Cell

Objective To investigate the influence of captoprial and SNP on the release of ET -1 in cultured VSMC of rats. Methods Measurement of endothelin - 1 levels by radioimmljnoassay in various concentrations of captopril and/or sodium nitroprusside in cultured vascular smooth muscle cell (VSMC) of rats. Results Both captopril and SNP could reduce the high ET - 1 levels of VSMC which were caused by Ang Ⅱ. There was a linear relationship between Ang Ⅱlevels and ET -1 production ( r = 0. 760, P <0. 001 ) . Conclusion Endothelin - 1 may accelerate the formation and development of atherosclerosis through inhibiting endogenous NO production by VSMC. ACEI or NO inhibition of ET -1 release could reduce atherosclerosis formation.