Anti-lipid deposition effect of HMG-CoA reductase inhibitor, pitavastatin, in a rat model of hypertension and hypercholesterolemia

Autor: R. Taniguchi, K. Kamio, Susumu Sekine, Shinichi Kobayashi, Naoki Matsumoto, Yuko Takeba, Toshio Kumai, Shigeko Oonuma, Osamu Miyazu, Mamoru Tadokoro, Yu Koitabashi
Rok vydání: 2004
Předmět:
Male
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
Arteriosclerosis
Hyperlipidemias
Reductase
General Biochemistry
Genetics and Molecular Biology
Nitric oxide
Rats
Sprague-Dawley
chemistry.chemical_compound
Rats
Inbred SHR
Internal medicine
medicine.artery
Hyperlipidemia
medicine
Animals
Enzyme Inhibitors
General Pharmacology
Toxicology and Pharmaceutics
Pitavastatin
Aorta
biology
Cholesterol
food and beverages
nutritional and metabolic diseases
General Medicine
medicine.disease
Dietary Fats
Rats
Disease Models
Animal
NG-Nitroarginine Methyl Ester
medicine.anatomical_structure
Endocrinology
chemistry
Hypertension
HMG-CoA reductase
Quinolines
biology.protein
Drug Therapy
Combination
lipids (amino acids
peptides
and proteins)
Endothelium
Vascular
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase
medicine.drug
Zdroj: Life Sciences. 74:2129-2142
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2003.09.051
Popis: Since the rat is an atherosclerosis-resistant species, the study of atherosclerosis using rats is limited. The present study was undertaken to develop an atherosclerotic model in rats, to investigate the effect of nitric oxide (NO) inactivation and hyperlipidemia, and to evaluate the effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, on NO inactivation and on hyperlipidemia-induced changes in the cardiovascular system. Four-month-old male spontaneously hypertensive hyperlipidemic rats (SHHR) and Sprague-Dawley (SD) rats were used to study 1) the effect of the period of treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L) on high fat diet (HFD)-treated SHHR and SD rats, and 2) the effect of pitavastatin (Pit, 0.3 mg/kg/day) on the changes in the aorta of L-NAME- and HFD-treated SHHR and SD rats. L-NAME administration for 1 month then HFD feeding for 2 months markedly increased the deposition of lipids and the thickness of the endothelium in SHHR. Continuous L-NAME treatment with HFD produced severe injury and stripped of endothelium in both strains. The plasma total cholesterol of L-NAME + HFD-treated and L-NAME + HFD + Pit-treated SHHR was significantly higher than that of control SHHR. Lipid deposition, however, was comparatively less in the aorta of L-NAME + HFD + Pit-treated SHHR. The concentration of cholesterol in the aorta of control SHHR was significantly lower than that in the aorta of L-NAME + HFD-treated SHHR, whereas that of L-NAME + HFD + Pit-treated SHHR was the same as that in control SHHR. These data indicated that Pit blocked lipid deposition in the aorta of L-NAME + HFD treated SHHR without changing plasma lipid profiles. In conclusion, NO inactivation and HFD induce lipid deposition in the endothelium, and the HMG-CoA reductase inhibitor blocks the deposition in SHHR.
Databáze: OpenAIRE
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