Journal
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 84, Issue 8-9, Pages 835-845Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/Y06-036
Keywords
Rho-kinase; fasudil; hypercholesterolemia; hypertension; endothelial dysfunction
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Funding
- NIDDK NIH HHS [K01 DK085217] Funding Source: Medline
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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 center dot kg(-1)) were administered (s.c.) to rats to produce hypercholesterolemia and hypertension (mean arterial blood pressure > 120ammHg), 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 p22(phox) and 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 center dot kg(-1), p.o.) and atorvastatin (30 mg center dot 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 p22(phox), superoxide anion, and serum thiobarbituric acid reactive substances. The ameliorative effect of fasudil was prevented by L-NAME. In conclusion, fasudil-induced inhibition of Rho-kinase may improve hypercholesterolemia- and hypertension-induced endothelial dysfunction.
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