Fluvastatin attenuates diabetes-induced cardiac sympathetic neuropathy in association with a decrease in oxidative stress.
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.


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(2alpha) (PGF(2alpha)) 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 PGF(2alpha) levels compared with DM-VE rats (13.8+/-9.2 vs 175.0+/-93.9 ng/g tissue), although PGF(2alpha) 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.


CONCLUSIONS
FL ameliorates cardiac sympathetic neural dysfunction in DM rats in association with attenuation of increased myocardial oxidative stress.
Matsuki
Akira
A
Second Department of Internal Medicine, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Nozawa
Takashi
T
Igarashi
Norio
N
Sobajima
Mitsuo
M
Ohori
Takashi
T
Suzuki
Takayuki
T
Fujii
Nozomu
N
Igawa
Akihiko
A
Inoue
Hiroshi
H
D019797:3-Iodobenzylguanidine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006321:Heart / Q000000981:diagnostic imaging; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D014280:Triglycerides; D019797:3-Iodobenzylguanidine; D000077340:Fluvastatin; D015237:Dinoprost; D019255:NADPH Oxidases; C515768:Cyba protein, rat