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

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 770-774.

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

王燕, 张明升, 刘宇, 陈敏

山西医科大学药理教研室,太原 030001,山西

收稿日期:2010-06-14 修回日期:2010-07-15 出版日期:2010-07-26 发布日期:2020-09-15
作者简介:王燕,女,博士,讲师,研究方向:心血管药理学。Tel: 0351-4135079-8011 E-mail:butou1977@yahoo.com.cn
基金资助:
山西医科大学2008年青年基金资助项目(200841)

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

WANG Yan, ZHANG Ming-sheng, LIU Yu, CHEN Min

Department of Pharmacology, Shanxi Medical University,Taiyuan 030001, Shanxi,China

Received:2010-06-14 Revised:2010-07-15 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 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 5 mg·kg^-1·d^-1;(2)卡托普利组(n=6):SHR给予卡托普利 15 mg·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。

关键词: 奈比洛尔, 肾素-血管紧张素系统, 自发性高血压大鼠

Abstract: 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.

Key words: Nebivolol, Renin-angiotensin system, Spontaneously hypertensive rats

中图分类号:

王燕, 张明升, 刘宇, 陈敏. 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[J]. 中国临床药理学与治疗学, 2010, 15(7): 770-774.

WANG Yan, ZHANG Ming-sheng, LIU Yu, CHEN Min. Effect of nebivolol on circle and aortic renin-angiotensin system in spontaneously hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 770-774.

参考文献

[1] 杨万松,黄体纲,樊振旺. 高蔗糖诱发大鼠胰岛素抵抗和高血压机制实验研究[J]. 天津医药,1998,6 (4) : 229- 233.
[2] Lagami T, Murakami T, Higuchi K,et al. Role of vascular wall renin: intracellular and extracellular mechanism [J]. Blood Vessels,1991, 28(1/2/3): 217 -223.
[3] Numaguchi K, Egashira K, Takemuto M,et al. Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats [J]. Hypertens,1995,26: 957 - 962.
[4] 曹锦秀,张丽萍,高春林,等. 高血压与肾脏疾病中肾脏局部肾素-血管紧张素系统的激活及病理生理作用[J]. 中国临床药理学与治疗学,2009,14 (12):1436-1440.
[5] Van Bortel LM, Fici F, Mascagni F. Efficacy and tolerability of nebivolol compared with other antihypertensive drugs: a meta-analysis [J]. Am J Cardiovasc Drugs, 2008,8(1):35-44.
[6] Cockcroft J. A review of the safety and efficacy of nebivolol in the mildly hypertensive patient[J]. Vasc Health Risk Manag,2007,3(6):909-917.
[7] Jin M, Wilhelm MJ, Lang RE, et al. Endogenous tissue renin-angiotensin systems, from molecular biology to therapy [J]. Am J Med, 1988, 84 (3A):28-36.
[8] 易春涛,程晓曙,俞建华,等. 辛伐他汀对一氧化氮缺乏性高血压大鼠心脏局部肾素血管紧张素系统的影响[J]. 中国临床药理学与治疗学,2002, 7 (3) : 227-230.
[9] 冀凯宏,姜宗来,杨向群,等. 血管紧张素II在自发性高血压大鼠主动脉重建中的作用[J]. 中国病理生理杂志,2000,16 (3) :214.
[10] Morishita R, Gibbons GH, Ellison KE,et al. Evidence for direct local effect of angiotensin II in vascular hypertrophy in vivo gene t ransfer of angiotensin converting enzyme [J]. J Clin Invest, 1995, 94(3): 978-984.
[11] Veverka A, Salinas JL. Nebivolol in the treatment of chronic heart failure[J]. Vasc Health Risk Manag,2007,3(5):647-654.
[12] Altwegg LA, d'Uscio LV, Barandier C,et al. Nebivolol induces NO-mediated relaxations of rat small mesenteric but not of large elastic arteries [J]. J Cardiovasc Pharmacol,2000, 36(3):316-320.
[13] Weiss R. Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation[J].Vasc Health Risk Manag,2006,2(3):303-308.
[14] Wang Y, Zhang M, Liu Y,et al. Neither K+ channels nor PI3K/Akt mediates the vasodilative effect of nebivolol on different types of rat arteries [J]. J Cardiovasc Pharmacol Ther,2009, 14(4):332-338.
[15] 丛洪良,黄体钢,杨万松,等. 依那普利对肾性高血压大鼠RAS系统及NO影响的实验研究[J]. 高血压杂志, 2000,8(2):168-171.