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

摘要

Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of long-term 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 F_2α (PGF_2α) and NADPH oxidase subunit p22phox mRNA expression. Sympathetic neural function was quantified by autoradiography using 131I- and 125I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF_2α levels compared with DM-VE rats (13.8±9.2 vs 175.0±93.9 ng/g tissue), although PGF_2α levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22phox mRNA expression. Cardiac 131I-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