卡托普利早期治疗自发性高血压大鼠阻止遗传性高血压形成的机理

本文探讨早期卡托普利治疗阻止高血压形成的机制。自发性高血压大鼠（ＳＨＲ）宫内期给药（１００ｍｇ·ｋｇ－１·ｄ－１）到１６周龄，４０ｗｋ处死。测定收缩压，血管壁／腔面积比（Ｍ／Ｌ），血管收缩（后肢灌注Ｆｏｌｋｏｗ模型）和舒张（动脉环体外实验）功能。卡托普利治疗显著降低血压，停药后２４ｗｋ，血压仍维持在相对低的水平（２１．１±１．１ｋＰａ，对照２８．５±１．１ｋＰａ。Ｐ＜０．０１）．治疗能明显减少Ｍ／Ｌ并接近正常ＷＫＹ大鼠水平。治疗组ＳＨＲ大鼠主动脉对硝普钠舒张敏感性及最大舒张反应明显比８ＨＲ增高，后肢阻力血管苯福林灌注显示ＳＨＲ最小灌注压，最大灌注压，曲线最大斜率都明显比ＷＫＹ大，ＥＣ５０明显较小，治疗的ＳＨＲ以上四个指标几乎达到与ＷＫＹ相同水平。结论：卡托普利持久地阻止高血压形成，持久降压的机理可能是在抑制血管肥厚基础上，减弱末梢血管阻力，改善血管舒张功能。关键词

Mechanism to Prevent genetic hypertension by early captopriltreatment in spontaneously hypertensive rats 1

The mechanism of early captopril (Cap)treatment to prevent hypertension was explored. Cap(100 mg· kg-1· d-1) was administered orally tospontaneously hypertensive rats (SHR) from intrauterine pe-riod to 16 wk of age. Experiments were performed at 40 wkof age. Systolic blood pressure (fSBP) was measured.Vaseular medium and lumen ratio (M / L) was determinedby morphometric method. Functions of vascular contractionand relaxation were studied using hindquarter perfusion ofFolkow's model and aortic ring segment experiment in vitrorespectively. Early-onset Cap therapy significantly de-creased SBP. After discontinuance of treatment for 24 wk.SBP of Cap treated SHR (SHRcap) was still maintained atlower level than that of untreated SHR (21. 1±1. 1 vs 28.5 ±1.1 kpa, P<0.001). The M/L in various vesscls waspronouncedly reduced in the treated group and was almostidentical to the level of WistarKyoto (WKY) rats.Vasorelaxation sensitivity and maximum relaxation to so-dium nitroprusside in SHRcap thoracic aortas were morepronounced while compared with those in SHR. Hindquart-er perfusion with phenylephrine showed that minimum andmaximum perfusion pressure, maximum slope weresignificantly higher in SHR than in WKY rats. and therewas a lower EC50 in SHR than in WKY rats. No signifi-cant difference in above four indexes was found betweenSHRcap and WKY rats. Conclusion early treatment withCap in SHR prevented the development of hypertension.The effect of Cap to reduce blood pressure persistently afterwithdrawal of treatment might result frorn reducingperipheral vascular resistance and improving vasomotorfunction on the basis of inhibiting vascular hypertrophy per-manently.