Fluvastatin inhibits O 2 − and ICAM-1 levels in a rat model with aortic remodeling induced by pressure overload

Katoh, Makoto; Kurosawa, Yukie; Tanaka, Keiko; Watanabe, Ayako; Doi, Hisayoshi; Narita, Hiroshi

doi:10.1152/ajpheart.2001.281.2.h655

Cited by 19 publications

(17 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Statins decrease free radical generation in the vascular wall and myocardium, 39,40 and fluvastatin exerts potent antioxidant activities as a free radical scavenger, a property that is derived from its unique chemical structure. 21, 41 Thus, the present findings show that fluvastatin reduces cardiac oxidative stress in DM rats.…”

Section: Effects Of Fluvastatin On Cardiac Oxidative Stresssupporting

confidence: 61%

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Matsuki

Nozawa

Igarashi

et al. 2010

Circ J

View full text Add to dashboard Cite

Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of longterm treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats.Methods and Results: FL (10 mg · kg -1 · day -1 , DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F2α (PGF2α) and NADPH oxidase subunit p22 phox mRNA expression. Sympathetic neural function was quantified by autoradiography using 131 I- and 125 I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF2α levels compared with DM-VE rats (13.8±9.2 vs 175.0±93.9 ng/g tissue), although PGF2α levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22 phox mRNA expression. Cardiac 131 I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31±0.08, 1.88±0.22, and 1.58±0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. Diabetes-Induced Cardiac NeuropathyExperimental Animals DM was induced in male Wistar rats weighing 250-300 g by an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ, n=40). Non-DM control rats (n=14) were not injected with STZ. The rats with glucose levels >250 mg/dl at 1 week after STZ injection were considered diabetic (n=28) and used in the experiments. Two weeks later, fluvastatin (10 mg · kg -1 · day -1 , n=14) or vehicle (DM controls: 0.1% carboxymethyl cellulose, n=14) was orally administered by gavage for 2 weeks. Standard rat chow and tap water were provided ad libitum throughout the study.Systolic blood pressure and heart rate were measured using an indirect tail-cuff method (BP-98A, Softron) and lipid peroxides (LPO) in plasma were determined using a hemoglobin-methylene blue method that selectively detects the absolute quantity of LOOH. Cardiac oxidative stress was then assessed as the levels of 8-isoprostaglandin F2α (PGF2α) and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox mRNA expression, and cardiac sympathetic neural function was assessed using 131 I-and 125 Ilabeled MIBG.Radioactive MIBG Tracers FUJIFILM RI Pharma Co Ltd (Tokyo, Japan) prepared and supplied 131 I-and 125 I-labeled MIBG at a radiochemical purity >98%, and specific activity of 30-70 GBq/mmol. Cardiac MIBG AccumulationDual-tracer autoradiography proceeded as described. 22,23 Briefly, 0.37 MBq of 125 I-MIBG was injected via the external jugular vein under pentobarbital sodium anesthesia (30 mg/kg, ip). Two hours later, 1.85 MBq of 131 I-MIBG was intravenously injected and 30 min thereafter, the heart was removed and washed in cold saline. Specimens were frozen in isopentane, cooled in dry ice, embedded in methyl cellulose and cut in...

show abstract

Section: Effects Of Fluvastatin On Cardiac Oxidative Stresssupporting

confidence: 61%

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Matsuki

Nozawa

Igarashi

et al. 2010

Circ J

View full text Add to dashboard Cite

show abstract

“…Our results may provide insight into the basis of the effects of statins on vascular functions, and an additional scientific rationale for using these drugs to reduce cardiovascular mortality in patients with RA. We selected a 5-mg/kg daily dosage of fluvastatin because 5-10 mg/kg of this drug does not affect serum lipid levels in other disease models in rats (36)(37)(38). Indeed, levels of serum lipids were not changed by treatment with fluvastatin in our arthritis model.…”

Section: Discussionmentioning

confidence: 99%

Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant‐induced arthritis

Haruna

Morita

Yada

et al. 2007

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To investigate the effect of statins on vascular dysfunction in rat adjuvant-induced arthritis (AIA).Methods. Fluvastatin (5 mg/kg/day) was administered orally to rats with AIA, for 21 days after the onset of arthritis. The vasodilatory response to acetylcholine of aortic rings isolated from rats with AIA that were not treated or were treated with fluvastatin and from normal rats was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine in aortas were measured by Western blotting. In vitro and in situ superoxide production in aortas was evaluated based on fluorogenic oxidation of dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial nitric oxide synthase (eNOS) in aortas was examined by real-time reverse transcriptase-polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin, a critical eNOS cofactor, were determined by high-performance liquid chromatography.Results. Fluvastatin reversed endothelial dysfunction in AIA without affecting the clinical severity of arthritis or serum cholesterol concentration. Fluvastatin reduced the amounts of HNE and nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial cells and smooth muscle cells in the tissue, in rats with AIA. NADH-or L-arginine-induced superoxide production was not observed in the aortic samples from fluvastatin-treated rats with AIA. Fluvastatin decreased the levels of expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels of tetrahydrobiopterin were significantly reduced in rats with AIA, and were increased by administration of fluvastatin.Conclusion. Our findings demonstrate that fluvastatin has potent vascular protective effects in AIA and provide additional scientific rationale for the use of statins to reduce cardiovascular mortality in patients with rheumatoid arthritis.

show abstract

“…Fluvastatin treatment (10 mg/kg per d orally) was started 5 d before PAN injection and continued throughout the experiment. The dose was selected because fluvastatin at a dose of 10 mg/kg per d does not affect serum total cholesterol level in Sprague-Dawley rats (22). In some experiments, rats were treated with fasudil (Asahi Kasei, Tokyo, Japan), a Rho-kinase inhibitor (23).…”

Section: Animal Experimental Designmentioning

confidence: 99%

Fluvastatin Ameliorates Podocyte Injury in Proteinuric Rats via Modulation of Excessive Rho Signaling

Shibata

Nagase

Fujita

2006

Journal of the American Society of Nephrology

105

103

View full text Add to dashboard Cite

Fluvastatin inhibits O 2 − and ICAM-1 levels in a rat model with aortic remodeling induced by pressure overload

Cited by 19 publications

References 38 publications

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant‐induced arthritis

Fluvastatin Ameliorates Podocyte Injury in Proteinuric Rats via Modulation of Excessive Rho Signaling

Contact Info

Product

Resources

About