title: Effects of Xin-Ji-Er-Kang formula on 2K1C-induced hypertension and cardiovascular remodeling in rats.
abstract: BACKGROUND
  Xin-Ji-Er-Kang (XJEK), a Chinese herbal formula, is effective against hypertension induced coronary heart disease, viral myocarditis and toxic myocarditis. In this study, the effect of XJEK on cardiovascular system was investigated. To test the hypothesis that Xin-Ji-Er-Kang (XJEK) has an anti-hypertensive effect mediated through attenuation of cardiac remodeling, and amelioration of vascular endothelial dysfunction and oxidative stress.
  
  
  METHODS
  Hypertension was induced in Wistar rats by 2 kidney 1 clip (2K1C) treatment. The hypertensive rats were then randomly assigned into four groups and treated as follows: group 1 (Sham-operated [Sh-Op] group received only drinking water), group 2 (induced hypertensive model+no treatment), and group 3 (induced hypertensive+a single daily oral dose of 24 g kg(-1) XJEK treatment) and group 4 (induced hypertensive+a single oral dose of 15 mg kg(-1) Fosinopril treatment). The rats in all the defined groups were respectively treated for a period of 4 weeks. Cardiovascular parameter such as systolic blood pressure (SBP) was measured weekly by using tail-cuff apparatus; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the rate of the rise in left ventricular pressure (±dp/dt max) were measured by using a PowerLab 8/30 apparatus (AD Instruments, Australia) at the end of the 8th week; heart weight/body weight (HW/BW) was determined as an index of myocardial hypertrophy (MH). Hematoxylin and eosin (H&E) and Van Gieson (VG) stain were used to assess the cardio-histological changes. Colorimetric analysis was used to assay serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), nitric oxide (NO), and hydroxyproline (Hyp) contents in cardiac tissue. Angiotensin II (Ang II) content in serum was assessed by radioimmunoassay; tetrahydrobiopterin (BH4) content in cardiac tissue, BNP and endothelial NOS (eNOS) in serum were determined by using ELISA, and the protein expressions of c-Jun NH2-terminal kinase (JNK), P-JNK, p38, P-p38, and NADPH oxidases-2 (Nox-2) were measured by western blot.
  
  
  RESULTS
  XJEK therapy could impair the heart systolic and diastolic function, potently improve the heart weight index, inhibit the elevation of HW/BW ratio, and markedly ameliorate hemodynamic indices and vascular remodeling index. It has blunted the decrease of SOD, NO and the increase in MDA and Ang II serum contents, myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) compared to the hypertensive model group. It also reduced the serum content of Hyp while increased BH4 levels in cardiac tissue. In addition, the expressions of Nox-2, P-JNK and P-p38MAPK were all suppressed compared to the hypertensive model group. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting eNOS activities and enhancing the NO activity in serum.
  
  
  CONCLUSIONS
  The results of the present study show that XJEK attenuates 2K1C-induced hypertension in rats, which confirms our hypothesis that XJEK has an anti-hypertensive and cardiovascular remodeling effect via attenuation of cardiac remodeling and improvement of endothelial dysfunction and oxidative stress.
authors: Department of Pharmacology, Key Laboratory of Antiinflammation and Immunopharmacology of Ministry of Education, Basic Medical College, Anhui Medical University, Hefei 230032, China.
authors: Kun
authors: K
authors: Guo
authors: College of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors: Chao-zong
authors: CZ
authors: Lan
authors: Department of Pharmacology, Key Laboratory of Antiinflammation and Immunopharmacology of Ministry of Education, Basic Medical College, Anhui Medical University, Hefei 230032, China.
authors: Ting-ting
authors: TT
authors: Yu
authors: Department of Pharmacology, Key Laboratory of Antiinflammation and Immunopharmacology of Ministry of Education, Basic Medical College, Anhui Medical University, Hefei 230032, China.
authors: Ling-ling
authors: LL
authors: Huang
authors: Department of Pharmacy, the Second People׳s Hospital of Hefei City, Hefei 230011, China.
authors: Xing-hui
authors: XH
authors: Wang
authors: Department of Clinical Medicine, Lishui People׳s Hospital, Zhe Jiang 323000, China.
authors: Chen
authors: C
authors: Pan
authors: Department of Pharmacology, Key Laboratory of Antiinflammation and Immunopharmacology of Ministry of Education, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address: aydgs@126.com.
authors: Shan
authors: S
authors: Gao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010946:Plants, Medicinal; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D066253:Vascular Remodeling / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C000599569:xin-ji-er-kang
keywords: 2K1C; Cardiac remodeling; Endothelial dysfunction; Hypertension; Oxidative stress