Effects of traditional Chinese medicine Xin-Ji-Er-Kang formula on 2K1C hypertensive rats: role of oxidative stress and endothelial dysfunction

BMC Complementary and Alternative Medicine

Shan Gao⁴  Zhen Zhang²  Xing-hui Wang⁴  Ling-ling Huang⁴  Jian Wang¹  Chao-zong Lan¹  Han-chun Chen³  Kun Guo⁴  Ting-ting Yu⁴ 

[1] Department of Traditional Chinese medicine, College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China;Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China;Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu 215021, China;Department of Pharmacology, Key Laboratory of Antiinflammatory and Immunopharmacology of Education Ministry, Basic Medical College, Anhui Medical University, Hefei 230032, China

关键词: Cardiac remodeling;    Hypertension;    Renovascular;    Antioxidant;    Endothelial dysfunction;    Oxidative stress;   

Others  :  1221073
DOI  :  10.1186/1472-6882-13-173

 received in 2013-01-28, accepted in 2013-07-05,  发布年份 2013

【 摘 要 】

Background

XinJiErKang (XJEK), a Chinese herbal formula, is identified as an effective preparation to treat coronary heart disease and myocarditis. The aim of the study is to investigate the anti-hypertensive effects of XJEK by oral administration and also to find out whether the drug has any role in oxidative stress and vascular endothelial function.

Methods

Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) which reached a plateau after 4 weeks of surgery. Treatment of hypertensive rats (20 mmHg higher than basic systolic blood pressure) with XJEK (6, 12, 24 g/kg/day) and fosinopril (15 mg/kg/day) respectively by intragastric administration started 4 weeks after surgery and continued for 4 weeks. The sham-operated (Sh-Op) controls received drinking water. BP was monitored weekly using tail-cuff apparatus. At the end of 8 wk, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate of rise of left ventricular pressure (±dp/dtmax) were examined (PowerLab 8/30, AD Instruments, Australia). The myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes were investigated by hematoxylin and eosin (HE) and Van Gieson (VG) stain. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content in serum, contents of hydroxyproline (Hyp) in the ventricular tissue were assayed by xanthin oxidase method, thiobarbituric acid (TBA) method, Griess method and alkaline hydrolysis method, respectively. Angiotensin II (Ang II) content in serum was detected by radioimmunoasssay method.

Results

XJEK therapy potently improved cardiac function, inhibited myocardial hypertrophy, improved cardiac pathology change, decreased the myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA), reduced the content of Hyp in the left ventricular tissue, inhibited the decrease of SOD activity and increase of MDA, Ang II content in serum. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting endothelial-dependent vasodilation of thoracic aortic rings and enhancing the NO activity in serum.

Conclusions

These findings suggest that administration of XJEK possess protective effects against 2K1C induced hypertension and cardiac remodeling in rats, preserve NO activity and endothelial function.

【 授权许可】

   
2013 Yu et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Frohlich ED: State of the Art lecture. Risk mechanisms in hypertensive heart disease. Hypertension 1999, 34:782-789.
• [2]Lawes CM, Vander Hoorn S, Rodgers A: International Society of Hypertension, Global burden of blood-pressure-related disease, 2001. Lancet 2008, 371:1513-1518.
• [3]Basile DP, Donohoe DL, Phillips SA, Frisbee JC: Enhanced skeletal Muscle arteriolar reactivity to ANGII after recovery from ischemic acute renal failure. Am J Physiol Regul Integr Comp Physiol 2005, 289:1770-1776.
• [4]Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Oshima T, Chayama K: Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002, 346:1954-1962.
• [5]Garrido AM, Griendling KK: NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol 2009, 302:148-158.
• [6]Romero JC, Reckelhoff JF: State-of-the-Art lecture. Role of angiotensin and oxidative stress in essential hypertension. Hypertension 1999, 34:943-949.
• [7]Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S: Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol 2009, 157:527-536.
• [8]Toblli JE, DiGennaro F, Giani JF, Dominici FP: Nebivolol: impact on cardiac and endothelial function and clinical utility. Vasc Health Risk Manag 2012, 8:151-160.
• [9]Wang QM, Chen GL, Wang YJ, Wang HS, Gao MH, Gong YZ: An experimental study on inhibitory effect of xinjierkang granules on virus myocarditis. Zhongguo Zhong Yao Za Zhi 2000, 25:293-296.
• [10]Wang J, Cao EZ, Li LZ: Xin Ji Er Kang in coronary heart disease. Nanjing Zhong Yi Yao Da Xue Xue Bao 1998, 14:201-212.
• [11]Gao S, Wang XH, Huang LL, Yu TT: Effects of a compound Chinese medicine Xinjierkang on isoproterenol-induced ventricular remodeling in mice. J Chin Intergr Med 2012, 10:330-336.
• [12]Gao S, Huang LL, Wang XH, Yu TT, Du SM, Guo YW: Effects of Xinjierkang on two kidney one clip-induced hypertension and target organ injury in rats. J Chin Med Mat 2012, 35:591-595.
• [13]Gao S, Long CL, Wang RH, Wang H: K(ATP) activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function. Cardiovasc Res 2009, 83:444-456.
• [14]Wang XH, Huang LL, Yu TT, Zhu JH, Shen B, Zhang Y, Wang HZ, Gao S: Effects of Oligomeric grape seed Proanthocyanidins on heart, Aorta, Kidney in DOCA-Salt Mice: role of oxidative stress. Phytother Res 2012. Epubmed ahead of print
• [15]Veltkamp R, Rajapakse N, Robins G, Puskar M, Shimizu K, Busija D: Transient focal ischemia increases endothelial nitric oxide synthase in cerebral blood vessels. Stroke 2002, 33:2704-2710.
• [16]Wu YB, Shi LL, Wu YJ, Xu WH, Wang L, Ren MS: Protective effect of gliclazide on diabetic peripheral neuropathy through Drp-1 mediated-oxidative stress and apoptosis. Neurosci Lett 2012, 523:45-49.
• [17]Bell D, Kelso EJ, Argent CC, Lee GR, Allen AR, McDermott BJ: Temporal characteristics of cardiomyocyte hypertrophy in the spontaneously hypertensive rat. Cardiovasc Pathol 2004, 13:71-78.
• [18]Gupta S, Das B, Sen S: Cardiac hypertrophy: mechanisms and therapeutic opportunities. Antioxid Redox Signal 2007, 9:623-652.
• [19]Haider AW, Larson MG, Benjamin EJ, Levy D: Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death. J Am Coll Cardiol 1998, 32:1454-1459.
• [20]Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990, 322:1561-1566.
• [21]Guimaraes DA, Rizzi E, Ceron CS, Oliveira AM, Oliveira DM, Castro MM, Tirapelli CR, Gerlach RF, Tanus-Santos JE: Doxycycline dose-dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol 2011, 108:318-325.
• [22]Wenzel UO, Wolf G, Jacob I, Schwegler C, Qasqas A, Amann K, Helmchen U, Stahl RA: Beneficial and adverse renal and vascular effects of the vasopeptidase inhibitor omapatrilat in renovascular hypertensive rats. Nephrol Dial Transplant 2003, 18:2005-2013.
• [23]Kim S, Iwao H: Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 2000, 52:11-34.
• [24]Bendall JK, Cave AC, Heymes C, Gall N, Shah AM: Pivotal role of a gp91 (phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 2002, 105:293-296.
• [25]Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ: Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(-) and systolic blood pressure in mice. Circ Res 2001, 89:408-414.
• [26]Murdoch CE, Zhang M, Cave AC, Shah AM: NADPH oxidase-dependent redox signalling in cardia hypertrophy, remodelling and failure. Cardiovasc Res 2006, 71:208-215.
• [27]Takimoto E, Champion HC, Li M, Ren S, Rodriguez ER, Tavazzi B, Lazzarino G, Paolocci N, Gabrielson KL, Wang Y, Kass DA: Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load. J Clin Invest 2005, 115:1221-1231.
• [28]Saw CL, Yang AY, Cheng DC, Boyanapalli SS, Su ZY, Khor TO, Gao S, Wang J, Jiang ZH, Kong AN: Pharmacodynamics of Ginsenosides: antioxidant activities, activation of Nrf2 and potential synergistic effects of combinations. Chem Res Toxicol 2012, 25:1574-1580.
• [29]Wang D, Zhuang Y, Tian Y, Thomas GN, Ying M, Tomlinson B: Study of the effects of total flavonoids of Astragalus on atherosclerosis formation and potential mechanisms. Oxid Med Cell Longev 2012. Epubmed ahead of print
• [30]Wang Y, Bai L, He X: Scavenging action of shengmaiyin decoction on hydroxyl radical. Zhong guo Zhong Yao Za Zhi 1998, 23:45-47.