Inhibitory effects of Caveolin-1-mediated atorvastatin on vasoconstriction of interlobar renal artery in SHR rats

XIE Xiao-ping; ZHANG Hai-jun; GUO Yi-bin; ZHANG Xi; CHANG Yao-ming; BAO Jun-xiang

doi:10.3969/j.issn.1671-2390.2017.10.012

Journal of Clinical Nephrology > 2017 > 17(10): 624-630. > DOI: 10.3969/j.issn.1671-2390.2017.10.012

XIE Xiao-ping, ZHANG Hai-jun, GUO Yi-bin, ZHANG Xi, CHANG Yao-ming, BAO Jun-xiang. Inhibitory effects of Caveolin-1-mediated atorvastatin on vasoconstriction of interlobar renal artery in SHR rats[J]. Journal of Clinical Nephrology, 2017, 17(10): 624-630. DOI: 10.3969/j.issn.1671-2390.2017.10.012

Citation:

PDF (1060 KB)

Inhibitory effects of Caveolin-1-mediated atorvastatin on vasoconstriction of interlobar renal artery in SHR rats

Department of Aerospace Hygiene, the Fourth Military Medical University, Xi'an 710032, China

More Information

Received Date: July 17, 2017
Rev Recd Date: September 25, 2017
Available Online: May 11, 2023
Published Date: October 27, 2017

Graphical Abstract

Abstract

Abstract

Objective Excessive vasoconstriction of interlobar renal artery (IRA) is one of preliminary manifestations of renal damage in hypertension, during which caveolin-1 plays an important role. Atorvastatin (ATVS) represses cholesterol (CHO) synthesis to down-regulate the expression of caveolin-1, so we aimed to investigate whether the ATVS inhibited vasoconstriction of IRA to angiotensin Ⅱ (Ang Ⅱ) by regulating caveolin-1 in spontaneously hypertensive rats (SHR).Methods Twelve SHR were randomly divided into two groups:SHR control group, and SHR ATVS-treated group. Six Wistar Kyoto (WKY) rats weighing the same were employed as control group. Systolic blood pressure (SBP) was measured with the tail-cuff technique before and 2 or 4 weeks after ATVS treatment. Isometric force recording system was used to detect the vascular function. Western blotting was conducted to examine the protein abundance of caveolin-1 or angiotensin Ⅱ type 1 receptor (AT₁). Immumoprecipitation was carried out to assess the binding of caveolin-1 and AT₁.Results SBP, and intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ were significantly increased in SHR as compared to WKY rats (P<0.05). At 4th week, ATVS treatment could significantly reduce SPB(P<0.05), and the intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ (P<0.05) in SHR control group. Meanwhile, the protein expression of caveolin-1 or AT₁ as well as Ang Ⅱ elicited binding of caveolin-1 or AT₁ in IRA was higher in SHR than in WKY rats, which could also be reduced by ATVS (P<0.05). The ex vivo incubation of CHO raised the caveolin-1 protein content and promoted the binding of caveolin-1 and AT₁ in IRA of ATVS-treated SHR (P<0.05). At the same time, CHO enhanced the intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ (P<0.05).Conclusions ATVS mitigated the vasoconstriction of IRA to Ang Ⅱ in SHR, which was mediated by reducing caveolin-1 expression and inhibiting the binding of caveolin-1 and AT₁.
- Atorvastatin,
- Hypertension,
- Angiotensin Ⅱ,
- Caveolin-1

FullText(HTML)

References (30)

References

[1]	Tozawa M, lseki K, Iseki C, et al. Blood pressure predicts risk of developing en-stage renal disease in men and women[J]. Hypertension, 2003, 41(6):1341-1345.
[2]	Protasiewicz M, Kadziela J, Poczatek K, et al. Renal artery stenosis in patients with resistant hypertension[J]. Am J Cardiol, 2013, 112(9):1417-1420.
[3]	Te RL, van Esch JH, Roks AJ, et al. Hypertension:renin-angiotensin-aldosterone system alterations[J]. Circ Res, 2015,116(6):960-975.
[4]	王双, 万载阳, 唐朝克, 等. 两肾一夹型高血压大鼠重塑血管对血管紧张素Ⅱ反应变化及其机制[J]. 中国动脉硬化杂志, 2003, 11(6):501-504.
[5]	张海军, 张茜, 谢小萍, 等. 平滑肌细胞caveolae在自发性高血压大鼠肾叶间动脉收缩功能改变中的作用研究[J]. 临床肾脏病杂志, 2016, 16(10):625-631.
[6]	张海军, 苏玉婷, 孟星星, 等. 平滑肌细胞caveolae在大鼠肾动脉收缩反应调控中的作用研究[J]. 临床肾脏病杂志, 2016, 16(7):432-438.
[7]	Callera GE, Montezano AC, Yogi A, et al. Vascular signaling through cholesterol-rich domains:implications in hypertension[J]. Curr Opin Nephrol Hypertens, 2007, 16(2):90-104.
[8]	Wang Z, Bai Y, Yu J, et al. Caveolae regulate vasoconstriction of conduit arteries to angiotensin Ⅱ in hindlimb unweighted rats[J]. J Physiol, 2015, 593(20):4561-4574.
[9]	Razani B, Lisanti MP. Caveolins and caveolae:molecular and functional relationships[J]. Exp Cell Res, 2001, 271(1):36-44.
[10]	Krane V, Wanner C. Statins, inflammation and kidney disease[J]. Nat Rev Nephrol, 2011,7(7):385-397.
[11]	谢晓竞, 杨解人, 王安才. 阿托伐他汀的降血压作用及其机制实验研究[J]. 中华全科医学, 2008, 6(9):882-884, 封3.
[12]	Taylor FC, Huffman M, Ebrahim S. Statin therapy for primary prevention of cardiovascular disease[J]. JAMA, 2013, 310(22):2451-2452.
[13]	郑颖, 吕明睿. 阿托伐他汀改善高血压患者早期肾损害的研究[J]. 中外健康文摘, 2012, 40:132-133.
[14]	Sinatra ST, Teter BB, Bowden J, et al. The cholesterol and statin controversy:the new 2013 statin-cholesterol guidelines[J]. Altern Ther Health Med, 2014, 20(5):14-17.
[15]	Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage:implications for therapy[J]. Hypertension, 2004, 44(5):595-601.
[16]	许红强, 王金萍, 常丽娜. 肾叶间动脉阻力指数与原发性高血压早期肾损害的相关性[J]. 安徽中医学院学报, 2006, 25(4):51-52.
[17]	张雯, 马克涛, 刘卫东, 等. 缝隙连接在自发性高血压大鼠肾叶间动脉收缩增强中的作用[J]. 安徽医科大学学报, 2014, 49(11):1570-1573.
[18]	Burnier M, Brunner HR. Angiotensin Ⅱ receptor antagonists[J]. Lancet, 2000, 355(9204):637-645.
[19]	阮志芹, 李华. 原发性高血压和肾功能减退的相关性[J]. 中华高血压杂志, 2017, 1:22-26.
[20]	张志杰, 胡申江, 孙坚, 等. 阿托伐他汀对自发性高血压大鼠血管内皮功能的保护作用[J]. 浙江大学学报(医学版), 2007, 36(4):355-359.
[21]	Li CL, Chou HW, Chan KA, et al. Effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes mellitus[J]. Am J Cardiol, 2015, 115(5):619-624.
[22]	Chang CH, Lee YC, Tsai CT, et al. Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease[J]. Atherosclerosis, 2014, 232(1):224-230.
[23]	焦海霞, 李凌, 余涓, 等. 尾套法和颈动脉法测定急性应激大鼠血压变化值的比较[J]. 福建医科大学学报, 2006, 40(4):404-405.
[24]	张勤勤, 孙润广, 李连启. Caveolae及其蛋白家族的生物学结构和功能的研究现状[J]. 北京生物医学工程, 2011, 30(2):215-220.
[25]	Yin X, Li B, Chen H, et al. Differential signaling pathways in angiotensin Ⅱ-and epidermal growth factor-stimulated hepatic C9 cells[J]. Mol Pharmacol, 2008, 74(5):1223-1233.
[26]	Linder AE, Thakali KM, Thompson JM, et al. Methyl-beta-cyclodextrin prevents angiotensin Ⅱ-induced tachyphylactic contractile responses in rat aorta[J]. J Pharmacol Exp Ther, 2007, 323(1):78-84.
[27]	Busija AR, Patel HH, Insel PA. Caveolins and cavins in the trafficking, maturation, and degradation of caveolae:implications for cell physiology[J]. Am J Physiol Cell Physiol, 2017, 312(4):C459-C477.
[28]	Raghow R. Statins redux:a re-assessment of how statins lower plasma cholesterol[J]. World J Diabetes, 2017, 8(6):230-234.
[29]	Guasti L, Marino F, Cosentino M, et al. Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin Ⅱ type 1 receptor expression:1-year follow-up[J]. Eur Heart J, 2008, 29(9):1118-1126.
[30]	Nickenig G, Baumer AT, Temur Y, et al. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men[J]. Circulation, 1999, 100(21):2131-2134.

Cited By

Get Citation

PDF

XML

Article views (313) PDF downloads (279)

Turn off MathJax

Article Contents

Abstract

References

Inhibitory effects of Caveolin-1-mediated atorvastatin on vasoconstriction of interlobar renal artery in SHR rats

Abstract

References

Catalog

Export File

Citation

Format

Content