Department of Pharmacology
Department of Pathology and Molecular Medicine
Department of Cardiology
Department of Pharmacology
Department of Cellphysiology, Akita University School of Medicine, Akita
Department of Anesthesiology
Department of Anesthesiology
Department of MolecularPharmacology, Tohoku University School of Medicine
Department of Cardiology
Department of Pharmacy, Hirosaki University, Graduate School of Medicine
Department of Anesthesiology
Department of Metabolism and Diabetes, Tohoku Medical Pharmaceutical University
Department of Pathology and Molecular Medicine
Department of Pharmacology
抄録
Persistent hyperglycemia is implicated in the pathogenesis of chronic diabetic complications, such as
neuropathy. Therefore, we investigated Electrocardiogram( ECG)-related changes, including various ECG parameters
and heart rate variability, and neuropathic changes in diabetic Goto-Kakizaki (GK) rats, a spontaneous model for
type 2 diabetes. GK rats (50 weeks old) showed increased plasma glucose and decreased R-R interval variability,
which was likely due to diabetic polyneuropathy in the autonomic nervous system. Interestingly, GK rats showed a
decreased baroreflex compared with control Wistar rats. Furthermore, GK rats showed limited fluctuation changes
in beat-to-beat dynamics. In the frequency domain analysis, the low-frequency component was similar but the highfrequency
component was significantly decreased in GK rats, suggesting decreased parasympathetic nerve regulation
and conserved sympathetic nerve regulation. In addition, GK rats showed a limited response to high-dose atropine, a
muscarinic receptor antagonist, indicating modified parasympathetic nerve regulation in GK rats. Our data strongly
suggests that GK rat could be a nice animal model for chronic cardiovascular disease related to diabetic neuropathy.