Effect of fasudil on macrovascular disorder-induced endothelial dysfunction.

Effect of fasudil on macrovascular disorder-induced endothelial dysfunction.
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法舒地尔对大血管疾病引起的内皮功能障碍的影响。

DOI:
10.1139/y06-036
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发表时间:
2006
影响因子:
2.1
通讯作者:
Singh,Manjeet
Singh,Manjeet
中科院分区:
医学4区
文献类型:
--
作者:
Shah,DhvanitI;Singh,Manjeet

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本研究旨在探讨法舒地尔(Rho激酶抑制剂)在高胆固醇血症和高血压诱导的内皮功能障碍中的作用。高脂饲料(8周)和醋酸脱氧可的松(DOCA)(40 mg·kg-1)皮下注射(s.c.)致大鼠分别产生高胆固醇血症和高血压(平均动脉血压> 120 mmHg)。采用离体主动脉环、胸主动脉电子显微镜和血清亚硝酸盐/硝酸盐浓度评估内皮功能障碍。RT-PCR检测p22 phox和eNOS mRNA的表达。测定血清硫代巴比妥酸反应物质浓度和主动脉超氧阴离子浓度,以评估氧化应激。法舒地尔30 mg·kg-1,p.o.阿托伐他汀(30 mg·kg-1,p.o.)治疗明显防止高胆固醇血症和高血压引起的乙酰胆碱诱导的内皮依赖性舒张的衰减,血管内皮衬里的损伤,eNOS mRNA表达和血清亚硝酸盐/硝酸盐浓度的降低,以及p22 phox、超氧阴离子和血清硫代巴比妥酸反应性的mRNA表达的增加。 物质. L-NAME可阻断法舒地尔的改善作用。总之,法舒地尔诱导的Rho激酶抑制可改善高胆固醇血症和高血压诱导的内皮功能障碍。
The present study has been designed to investigate the effect of fasudil (Rho-kinase inhibitor) in hypercholesterolemia- and hypertension-induced endothelial dysfunction. High fat diet (8 weeks) and desoxycortisone acetate (DOCA) (40 mg·kg–1) were administered (s.c.) to rats to produce hypercholesterolemia and hypertension (mean arterial blood pressure > 120 mmHg), respectively. Endothelial dysfunction was assessed using isolated aortic ring, electron microscopy of thoracic aorta, and serum concentration of nitrite/nitrate. The expression of mRNA for p22phoxand eNOS was assessed by using RT-PCR. Serum thiobarbituric acid reactive substances concentration and aortic superoxide anion concentration were estimated to assess oxidative stress. Fasudil (30 mg·kg–1, p.o.) and atorvastatin (30 mg·kg–1, p.o.) treatments markedly prevented hypercholesterolemia- and hypertension-evoked attenuation of acetylcholine-induced endothelium-dependent relaxation, impairment of vascular endothelial lining, decrease in expression of mRNA for eNOS and serum nitrite/nitrate concentration, and an increase in expression of mRNA for p22phox, superoxide anion, and serum thiobarbituric acid reactive substances. The ameliorative effect of fasudil was prevented byL-NAME. In conclusion, fasudil-induced inhibition of Rho-kinase may improve hypercholesterolemia- and hypertension-induced endothelial dysfunction.
原发性高血压的氧化应激。
DOI: 10.2174/1381612043384619
发表时间: 2004
影响因子: 3.1
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Francesco Portaluppi;B. Boari;Roberto Manfredini
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发表时间: 1999-06-10
期刊: NATURE
影响因子: 64.8
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影响因子: 10.8
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发表时间: 2001-06-01
影响因子: 15.9
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DOI: 10.1161/01.cir.100.14.1494
发表时间: 1999-10-05
期刊: CIRCULATION
影响因子: 37.8
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Azumi, H;Inoue, N;Yokoyama, M
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