氢氯噻嗪和吲哒帕胺逆转自发性高血压大鼠心肌肥厚及促进心肌中内皮型一氧化氮合酶的表达

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (5): 528-531.

氢氯噻嗪和吲哒帕胺逆转自发性高血压大鼠心肌肥厚及促进心肌中内皮型一氧化氮合酶的表达

何燕, 钟国强, 王炎, 涂荣会, 汪道文¹

广西医科大学第一附属医院老年心血管内科,心血管研究所,南宁 530000,广西;
¹ 华中科技大学同济医学院附属同济医院心血管内科, 武汉 430000,湖北

收稿日期:2006-02-11 修回日期:2006-03-03 出版日期:2006-05-26 发布日期:2020-12-09
通讯作者: 汪道文, 男, 博士生导师, 研究方向:分子心脏病学。 E-mail:dwwang @tjh.tjmu.edu.cn
作者简介:何燕, 女, 硕士研究生, 研究方向:分子心脏病学。 Tel:13877109677 　 E-mail:hyxjwxy @126.com

Effects of hydrochlorothiazide and indapamide on left ventricular hyper-trophy and eNOS expression in spontaneous hypertensive rats

HE Yan, ZHONG Guo-qiang, WANG Yan¹, TOU Rong-hui, WANG Dao-wen¹

Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Jiangsu, China;
¹Cardiovascular Division of Internal Medicine Department and Gene Therapy Center, Tongji Medical College of Hua-zhong University of Science and Technology, Wuhan 430000, Hubei, China

Received:2006-02-11 Revised:2006-03-03 Online:2006-05-26 Published:2020-12-09

摘要/Abstract

摘要： 目的: 研究氢氯噻嗪和吲哒帕胺对肥厚心肌及心肌中内皮型一氧化氮合酶(endothelial nitric ox-ide synthase, eNOS)表达的影响, 从而探讨其逆转心肌肥厚可能的分子机制。 方法: 15 只成年雌性自发性高血压大鼠(SHR)随机分为对照组、氢氯噻嗪组、吲哒帕胺组。治疗前、开始至结束时每周测血压 1 次。4 周后处死动物, 取左心室称重后, 计算左心室重与体重的比值, 采用天狼猩红染色分析心肌间质和血管壁胶原分布。采用 Western Blot 法检测心肌 eNOS 蛋白质表达。 结果: 治疗组动物收缩压及左心室重与体重比均明显低于对照组。心肌经天狼猩红染色后见治疗组心肌结构基本正常, 与对照组相比未见明显的胶原沉积。并且治疗组在蛋白质水平显著上调心肌 eNOS 的表达(P<0.05)。结论: 吲哒帕胺或氢氯噻嗪治疗自发性高血压可逆转左室肥厚、上调心肌 eNOS、改善心肌纤维化从而起到保护心脏的作用。

关键词: 氢氯噻嗪, 吲哒帕胺, 自发性高血压大鼠, 左心室肥厚, 内皮型一氧化氮合酶

Abstract: AIM: To investigate the effects of hydro-chlorothiazide and indapamide on cardiac remodeling and the expression of endothelial nitric oxide synthase (eNOS) in spontaneous hypertensive rats (SHR).METHODS: Fifteen female SHRs were randomly divided into 3 groups (n =5):control group, hydrochlorothiazide(HCTZ, 10 mg·kg^-1 ·d^-1)group and indapamide (IND, 0.625 mg·kg^-1 ·d^-1)group.Systolic blood pressure (SBP)of the rats in each group was measured at pretreatment and each week during the study.Four weeks later, rats were sacrificed and the ratio of heart weight to body weight was calculated, collagen deposition in the heart was deter-mined histochemically using Sirius red staining, and eNOS protein expression of the heart was determined by Western blot.RESULTS: Both HCTZ and IND reduced the SBP of SHRs significantly (P<0.05).The drug group showed normal myocardium structure as compared with control rats which showed myocardium cell hypertro-phy, derangement, interstitial proliferation and mass col-lagen deposition.HCTZ and IND increased the eNOS ex-pression significantly.CONCLUSION: Both HCTZ and IND can protect the heart by reversing cardiac remodel-ing, upregulate the eNOS expression and reduce collagen deposition.

Key words: hydrochlorothiazide, indapamide, spon-taneous hypertensive rats, left ventricular hypertrophy, endothelial nitric oxide synthase

中图分类号:

R965.2

何燕, 钟国强, 王炎, 涂荣会, 汪道文. 氢氯噻嗪和吲哒帕胺逆转自发性高血压大鼠心肌肥厚及促进心肌中内皮型一氧化氮合酶的表达[J]. 中国临床药理学与治疗学, 2006, 11(5): 528-531.

HE Yan, ZHONG Guo-qiang, WANG Yan, TOU Rong-hui, WANG Dao-wen. Effects of hydrochlorothiazide and indapamide on left ventricular hyper-trophy and eNOS expression in spontaneous hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(5): 528-531.

参考文献

1 Schiffrin EL.A critical review of the role of endothelial factors in the pathogenesis of hypertension[J].J Cardiovasc Pharma-col, 2001;38:3-6
2 Ozaki M, Kawashima S, Yamashita T, Hirase T, Ohashi Y, Inoue N, et al.Overexpression of endothelial nitric oxide syn-thase attenuates cardiac hypertrophy induced by chronic isoprot-erenol infusion[J].Circ J, 2002;66:851-6
3 Lokhandwala Y, Damle A.Left ventricular hypertrophy in hy-pertensive patients in Indian primary care:prevalence and effect of treatment with sustained release indapamide[J].Curr Med Res Opin, 2004;20:639-44
4 涂荣会, 严江涛, 赵春霞, 何燕, 汪道文.利尿剂对高血压大鼠细胞色素 P450 表氧化酶及血管紧张素Ⅱ1型受体基因表达的影响[J].中华心血管病杂志, 2004;32:308-12
5 Rakic D, Rumboldt Z, Bagatin J, Polic S.Effects of four anti-hypertensive monotherapies on cardiac mass and function in hy-pertensive patients with left ventricular hypertrophy:randomized prospective study[J].Croat Med J, 2002;43:672-9
6 Yokoyama H, Averill DB, Brosnihan KB, Smith RD, Schiffrin EL, Ferrario CM.Role of blood pressure reduction in prevention of cardiac andvascular hypertrophy[J].Am J Hypertens, 2005; 18:922-9
7 Matter CM, Mandinov L, Kaufmann PA, Vassalli G, Jiang Z, HessOM.Effect of NO donors on LV diastolic function in pa-tients with severe pressure-overload hypertrophy[J].Circula-tion, 1999;99:2396-401
8 Numaguchi K, Egashira K, Takemoto M, Kadokami T, Shi-mokawa H, Sueishi K, et al.Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats[J]. Hypertension, 1995;26:957-62
9 Ozaki M, Kawashima S, Yamashita T, Hirase T, Ohashi Y, Inoue N, et al.Overexpression of endothelial nitric oxide syn-thase attenuates cardiac hypertrophy induced by chronic isoprot-erenol infusion[J].Circ J, 2002;66:851-6
10 Lu W, Liu PQ, Wang TH, Gong SZ, Fu SG, Pan JY.Role of mitogen-activated protein kinase in the inhibition of myocardial hypertrophy by nitric oxide in renovascular hypertensive rats[J]. Acta Physiol Sin, 2001;53:32-6

[1]	张俊秀, 沈媛媛, 杨解人, 郑书国, 郝伟. 联用芝麻素和维生素E抑制PI3K/AKT信号通路改善自发性高血压大鼠的左室纤维化[J]. 中国临床药理学与治疗学, 2020, 25(11): 1214-1222.
[2]	高艺文，张楠，吕婵梅，杨宣梅，岳桂华. 黄连解毒汤对幼龄自发性高血压大鼠血管内皮NO通路影响的研究[J]. 中国临床药理学与治疗学, 2019, 24(3): 248-253.
[3]	程小龙，胡坤媚，胡浩然，徐杭杭，杨解人，韩军. 中药玉夏胶囊对自发性高血压大鼠肾纤维化的作用研究[J]. 中国临床药理学与治疗学, 2018, 23(6): 632-639.
[4]	胡坤媚，胡浩然，沈媛媛，卢毅宁，杨解人，韩军. 中药玉夏胶囊对自发性高血压大鼠肾纤维化的改善作用及TGF-β₁ /Smads信号通路的影响[J]. 中国临床药理学与治疗学, 2017, 22(4): 387-393.
[5]	李忠洪，王平，周四桂，王桂香. 二甲双胍通过上调谷胱甘肽-S-转移酶μ₂抑制大鼠心肌肥厚[J]. 中国临床药理学与治疗学, 2017, 22(12): 1326-1331.
[6]	卢毅宁，沈媛媛，杨解人. 芝麻素对自发性高血压大鼠海马nNOS和NADPH氧化酶亚单位p22phox、p47phox蛋白表达的调节作用[J]. 中国临床药理学与治疗学, 2016, 21(9): 989-994.
[7]	宣佳利, 杨解人, 王欢, 姚海, 李伟, 赵梦秋, 韩军. 芝麻素联用维生素E对化学性肾损伤大鼠eNOS/iNOS表达的影响[J]. 中国临床药理学与治疗学, 2015, 20(1): 24-30.
[8]	姚海, 王欢, 马玉红, 张俊秀, 杨解人. 原花青素对D-半乳糖复合三氯化铝诱导大鼠主动脉损伤的保护作用及机制[J]. 中国临床药理学与治疗学, 2014, 19(4): 404-409.
[9]	薛婉婉, 洪华山, 林晓红, 林军华, 方美琴. 自发性高血压大鼠左室心肌壁内小动脉平滑肌瞬时受体电位通道的表达[J]. 中国临床药理学与治疗学, 2013, 18(8): 879-884.
[10]	刘艳, 杨解人, 郝伟, 张俊秀, 唐丽娟, 陈国祥. 复方山菊对自发性高血压大鼠主动脉损伤的保护作用及机制[J]. 中国临床药理学与治疗学, 2013, 18(7): 732-737.
[11]	黄晓晖, 王钦, 王鲲, 黄继汉, 裘福荣, 唐海沁, 李俊. 厄贝沙坦与氢氯噻嗪联用在大鼠体内剂量优化的定量研究[J]. 中国临床药理学与治疗学, 2012, 17(5): 521-528.
[12]	杜少陵, 杨解人, 张俊秀, 李文星. 芝麻素对自发性高血压大鼠肾病的保护作用[J]. 中国临床药理学与治疗学, 2012, 17(5): 502-507.
[13]	黄晓晖, 黄继汉, 陈纭, 裘福荣, 李俊, 孙瑞元. 厄贝沙坦与氢氯噻嗪联用在肾性高血压大鼠体内药动学-药效学关系研究[J]. 中国临床药理学与治疗学, 2012, 17(3): 294-301.
[14]	许珊, 梁宇光, 曲恒燕, 李媛媛, 高洪志, 郝光涛. HPLC-MS/MS法测定人体血浆中吲哒帕胺的浓度[J]. 中国临床药理学与治疗学, 2012, 17(2): 206-210.
[15]	万茜, 黄原原, 付志敏, 谭鸿毅, 裴奇, 黄志军, 阳国平. 奥美沙坦氢氯噻嗪片在中国健康志愿者体中的药代动力学[J]. 中国临床药理学与治疗学, 2011, 16(4): 393-399.