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

Abstract

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 p22^phox 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 p22^phox 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<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. Conclusions: FL ameliorates cardiac sympathetic neural dysfunction in DM rats in association with attenuation of increased myocardial oxidative stress. (Circ J 2010; 74: 468 - 475)