内皮素受体拮抗剂BMS-182874对高血压大鼠左心室和冠状动脉壁的影响

Effects of BMS 182874 on Left Ventricular Hypertrophy and Hypertrophy of Coronary Arteries in SHR

目的：研究内皮素受体Ａ（ＥＴＡ ）拮抗剂ＢＭＳ－１８２８７４ 对高血压大鼠左心室肥厚和冠状动脉管壁增厚的影响。 方法：研究于１９９７ 年１月～５ 月完成。４ 周龄大鼠设３组：分别为自发性高血压大鼠（ＳＨＲ组）、ＳＨＲ口服ＢＭＳ－１８２８７４（ＳＨＲ＋ Ｂ组）和正常血压大鼠（ＷＫＹ组），饲养１２周。 结果：ＳＨＲ＋ Ｂ组与ＳＨＲ组比较，收缩压、左心室重与体重比、冠状动脉外径大于１００ μｍ 的冠状动脉管壁横截面积及横截面积与内径比、平滑肌细胞的宽度及最大冠状动脉流量均无显著差异；冠状动脉外径小于１００ μｍ 的冠状动脉管壁横截面积及横截面积与内径比，ＳＨＲ＋ Ｂ组较ＳＨＲ组显著下降。血浆和心肌的ＥＴ含量：ＳＨＲ组与ＷＫＹ组无显著差异，ＳＨＲ＋ Ｂ组显著下降。 结论：ＥＴＡ 拮抗剂ＢＭＳ－１８２８７４治疗能部分预防ＳＨＲ外径小于１００ μｍ 冠状动脉管壁的增厚，但对ＳＨＲ大鼠高血压的形成、左心室和外径大于１００ μｍ 冠状动脉管壁的增厚及平滑肌细胞的肥大无明显的影响。

Objective:To study effects of endothelin receptor type A(ET A)antagonist(BMS 182874)on left ventricular hypertrophy and hypertrophy of coronary arteries in spontaneously hypertensive rats(SHR). Methods:Four week old rats were divided into three groups:untreated SHR,SHR treated with BMS 182874(SHR+B)and normotensive Wistar Kyoto rats(WKY).The rats were raised for 12 weeks. Results:Systolic blood prssure,left ventricle weight to body weight ratio and maximal coronary flow were similar between SHR+B and SHR.Size of vascular smooth muscle cells,Cross sectional area(CSA)and CSA to lumen diameter ratio(CSA/LD)of coronary arteries with outer diameter more than 100 μm were not significantly different in SHR+B and SHR,but CSA and CSA/LD of coronary arteries with outer diameter less than 100 μm greatly decreased in SHR+B compared SHR.Plasma and myocardia immunoreactive endothelin concentration was similar between SHR and WKY and reduced significantly in SHR+B compared with SHR. Conclusion:ET A antagonist could partly prevent hypertrophy of coronary arteries with outer diameter less than 100 μm in SHR,but could not effect on formation of hypertension,left ventricular hypertrophy and hypertrophy of coronary arteries with outer diameter more than 100 μm.