缓激肽B2受体在缬沙坦抑制心肌细胞肥大中的作用研究

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (4): 427-431.

缓激肽B₂受体在缬沙坦抑制心肌细胞肥大中的作用研究

赵艳峰, 徐江, 郑亚萍, 王虹¹, 屈雪菊²

武汉大学医学院生理学系, ¹中南医院老年病研究所,²湖北省过敏及免疫相关疾病重点实验室, 武汉430071, 湖北

收稿日期:2005-11-03 修回日期:2005-12-15 出版日期:2006-04-26 发布日期:2020-12-08
通讯作者: 徐江, 男, 硕士生导师, 主要从事高血压冠心病的研究。E-mail:xjiang88@yahoo.com
作者简介:赵艳峰, 女, 硕士研究生, 主要从事高血压心肌肥厚的研究。Tel:027-87331345 　E-mail:douzi1125@yahoo.com

Role of bradykinin B₂ receptor in AT₁ antagonist inhibition of Ang Ⅱ-induced cardiomyocyte hypertrophy in neonatal rats

ZHAO Yan-feng, XU Jiang, ZHENG Ya-ping, WANG Hong¹, QU Xue-ju²

Department of Physiology, WuhanUniversity School of Medicin, Wuhan 430071, Hubei, China;
¹Department of Geriatric Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China;
²Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan 430071, Hubei, China

Received:2005-11-03 Revised:2005-12-15 Online:2006-04-26 Published:2020-12-08

摘要/Abstract

摘要： 目的:探讨缓激肽(BK) B₂受体在缬沙坦(valsartan)抑制血管紧张素Ⅱ(Ang Ⅱ) 诱导的新生大鼠心肌细胞肥大中的作用及可能机制。方法:经差速贴壁法获得新生大鼠心肌细胞, 随机分为对照组、Ang Ⅱ组、缬沙坦组、Ang Ⅱ +缬沙坦组、Hoe-140 组和Ang Ⅱ +缬沙坦+Hoe-140 组。采用流式细胞仪技术检测细胞大小和蛋白含量, 硝酸还原酶法测定上清液中NO 含量, 放射免疫法测定细胞内cGMP 水平。结果:与对照组相比, 10^-7mol·L^-1 Ang Ⅱ显著增加心肌细胞大小和蛋白含量, 降低心肌细胞NO 生成(P<0.01), 10^-5mol·L^-1缬沙坦显著降低Ang Ⅱ诱导的心肌细胞肥大和蛋白合成增加(P <0.01), 促进心肌细胞NO(P <0.05) 和cGMP 生成(P <0.01), BKB2 受体阻断剂Hoe-140 可部分阻断缬沙坦的上述作用。结论:BK B₂受体部分介导了缬沙坦抑制心肌细胞肥大的效应, 该作用与NO 、cGMP 生成有关。

关键词: 缓激肽, 缓激肽B₂ 受体, 缬沙坦, 血管紧张素Ⅱ, 心肌细胞, 一氧化氮, 环磷酸鸟苷

Abstract: AIM: To investigate the role of the bradykinin (BK) B₂ receptor in the inhibitory effect of valsartan on angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy.METHODS: Neonatal rat cardiomyocytes were randomly divided into 6 groups:control, Ang Ⅱ, valsartan, Ang Ⅱ +valsartan, Hoe-140 (a specific BK B₂ receptor antagonist) and Ang Ⅱ +valsartan +Hoe-140. Flow cytometry (FCM) was used to evaluate the size and protein content of cardiomyocytes.Nitric oxide (NO) and intracellular cyclic GMP (cGMP) were measured by colorimetry and radioimmunoassay. RESULTS: 10 ^-7 mol·L ^-1 Ang Ⅱ significantly increased the size and protein content of cardiomyocytes compared to control (P < 0.01 for both), which was inhibited by 10 ^-5 mol·L ^-1 valsartan (P <0.01).10 ^-6 mol·L ^-1 Hoe-140 partially blocked the inhibitory effects of valsartan (P <0.05 or P <0.01 vs.Ang Ⅱ +valsartan, respectively).In the Ang Ⅱgroup, NO was markedly decreased (P <0.01 vs. control);valsartan significantly increased NO and intracellular cGMP compared to the Ang Ⅱgroup (P <0.01 for both), and the effect of valsartan was attenuated by Hoe-140 (P <0.01 or P <0.05 vs.Ang Ⅱ +valsartan, respectively).CONCLUSION: The BK B₂ receptor may partially mediate the antihypertrophic action of valsartan in Ang Ⅱ-induced cardiomyocyte hypertrophy, and the elevation of NO and cGMP may contribute to the cardioprotective effects of BK.

Key words: bradykinin, bradykinin B₂ receptor, valsartan, angiotensin Ⅱ, cardiomyocyte, NO, cGMP

中图分类号:

R972
R361.3

赵艳峰, 徐江, 郑亚萍, 王虹, 屈雪菊. 缓激肽B₂受体在缬沙坦抑制心肌细胞肥大中的作用研究[J]. 中国临床药理学与治疗学, 2006, 11(4): 427-431.

ZHAO Yan-feng, XU Jiang, ZHENG Ya-ping, WANG Hong, QU Xue-ju. Role of bradykinin B₂ receptor in AT₁ antagonist inhibition of Ang Ⅱ-induced cardiomyocyte hypertrophy in neonatal rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(4): 427-431.

参考文献

1 Yasunari K, Maeda K, Nakamura M, Watanabe T, Yoshikawa J, Hirohashi K.Left ventricular hypertrophy and angiotensin Ⅱ receptor blocking agents[J].Curr Med Chem Cardiovasc Hematol Agents, 2005;3:61-7
2 Crissman HA, Darzynkiewicz Z, Tobey RA, Steinkamp JA.Normal and perturbed Chinese Hamster Ovary cells:correlation of DNA, RNA and protein content by Flow cytometry[J].J Cell Biol, 1985;101:141-7
3 Booz GW.Putting the brakes on cardiac hypertrophy.Exploiting the NO-cGMP counter-regulatory system [J].Hypertension, 2005;45:341-6
4 Campbell DJ, Krum H, Esler MD.Losartan increases bradykinin levels in hypertensive humans[J].Circulation, 2005;111:315-20
5 Yang XP, Liu YH, Mehta D, Cavasin MA, Shesely E, Xu J, et al.Diminished cardioprotective response to inhibition of angiotensin-converting enzyme and angiotensin II type 1 receptor in B₂ kinin receptor gene knockout mice[J].Circ Res, 2001;88: 1072-9
6 Xu J, Carretero OA, Liu YH, Shesely E, Yang F, Kapke A, et al.Role of AT₂ receptors in the cardioprotective effect of AT₁ antagonists in mice[J].Hypertension, 2002;40:244-50
7 Liu YH, Xu J, Yang XP, Yang F, Shesely E, Carretero OA, et al.Effect of ACE inhibitors and Angiotensin Ⅱ type 1 receptor antagonists on endothelial NO synthase knockout mice with heart failure [J].Hypertension, 2001;39:375-81
8 Leeb-Lundberg LMF,Marceau F, Muller-Esterl W, Pettibong DJ, Zuraw BL.International union of pharmacology.XLV.Classification of the kinin receptor family:from molecular mechanisms to pathophysiological consequences[J].Pharmacol Rev, 2005; 57:27-77
9 Perez M, Adam A, Molinaro G.Bradykinin, an important mediator of the cardiovascular effects of metallopeptidase inhibitors: experimental and clinical evidences[J].J Clinical Basic Cardiol, 2001;4:39-46
10 Schmaier AH.The kallikrein-kinin and the rennin-angiotensin systems have a multilayered interaction [J].Am J Physiol Regul Integr Comp Physiol, 2003;285:R1-3
11 Rosenkranz AC, Hood SG,Woods RL, Dusting GJ, Ritchie RH. Acute antihypertrophic actions of bradykinin in the rat heart.Importance of cyclic GMP [J].Hypertension, 2002;40:498-503
12 Hornig B, Kohler C, Schlink D, Tatge H, Drexler H.AT₁-receptor antagonism improves endothelial function in coronary artery disease by a bradykinin/B₂-receptor-dependent mechanism[J]. Hypertension, 2003;41:1092-5
13 Hiyoshi H, Yayama K, Takano M, Okamoto H.Stimulation of cyclic GMP production via AT₂ and B₂ receptors in the pressureoverloaded aorta after banding [J].Hypertension, 2004;43:1258-63
14 Tschope CT, Spillmann F, Altmann C, Koch M,Westermann D, Dhayat N, et al.The bradykinin B1 receptor contributes to the cardioprotective effects of AT₁ blockade after experimental myocardial infarction [J].Cardiovasc Res, 2004;61:559-69

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缓激肽B₂受体在缬沙坦抑制心肌细胞肥大中的作用研究

Role of bradykinin B₂ receptor in AT₁ antagonist inhibition of Ang Ⅱ-induced cardiomyocyte hypertrophy in neonatal rats

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