奈比洛尔对自发性高血压大鼠循环和主动脉肾素-血管紧张素系统的影响

目的：探讨奈比洛尔（Nebivolol）对自发性高血压大鼠循环和主动脉肾素-血管紧张素系统（RAS）的影响。方法：18只自发性高血压大鼠（SHR）和6只同源正常血压大鼠Wistar-Kyoto（WKY）随机分为：（1）奈比洛尔组（n=6）：SHR给予奈比洛尔5mg·kg-1·d-1;（2）卡托普利组（n=6）：SHR给予卡托普利15mg·kg-1·d-1;（3）SHR对照组（n=6）;（4）WKY对照组（n=6）。奈比洛尔、卡托普利溶于蒸馏水中灌胃,对照组给予等体积蒸馏水灌胃。给药8周后测定血浆肾素活性（PRA）,血浆和主动脉血管紧张素Ⅱ（AngⅡ）、一氧化氮（NO）浓度,NO/AngⅡ和血管紧张素转化酶（ACE）活性。结果：与WKY比较,SHR血浆和主动脉NO含量降低,AngⅡ水平显著增加,NO/AngⅡ降低;主动脉ACE活性明显增加,而血浆ACE活性则降低;但PRA在两组间无显著性差异。奈比洛尔治疗对SHR血浆AngⅡ含量和ACE活性无影响,但可降低主动脉AngⅡ水平,抑制主动脉ACE活性,从而增加血浆及主动脉NO含量和NO/AngⅡ。结论：奈比洛尔抑制肾素-血管紧张素系统,可能是其降低血压的机制之一。

Effect of nebivolol on circle and aortic renin-angiotensin system in spontaneously hypertensive rats

AIM：To study the effect of nevilolol on circle and aortic renin-angiotensin system （RAS） in spontaneously hypertensive rats （SHR）. METHODS： SHR and age-matched Wistar-Kyoto （WKY） rats were randomly divided into 4 groups： （1） Nebivolol group（n=6）： SHR were treated with nebivolol（5 mg·kg-1·d-1, i.g.）; （2） Captopril group （n=6）： SHR were treated with captopril （15 mg·kg-1·d-1, i.g.）; （3） SHR control group （n=6）： SHR were treated with vehicle once daily, i.g.; （4） WKY control group （n=6）： WKY were treated with vehicle once daily, i.g. The therapy was continued for 8 weeks. At the end of this study, animals were anesthetized with 3% sodium pentobarbital （30 mg/kg, i.p.）. Plasma renin activity （PRA） was measured. Plasma and aortic nitric oxide （NO）, angiotensin Ⅱ（AngⅡ）, NO/AngⅡ and angiotnesin converting enzyme（ACE ） activity were also measured. RESULTS：Compared with WKY, the levels of NO, NO/AngⅡin plasma and aortic were lowered, while the level of AngⅡ was increased in SHR. ACE activity in aorta form SHR were increased than those in WKY, but plasma ACE activity was reduced. There was no difference in PRA between SHR and WKY. Nebivolol did not affect plasma AngⅡand ACE activity. But nebivolol reduced aortic AngⅡ concentration and inhibited aortic ACE activity. Nebivolol could increase the levels of plasma and aortic NO and NO/AngⅡ in SHR. CONCLUSION： The antihypertensive effect of nebivolol in SHR is accompanied by the inhibition of RAS.