Modified parasympathetic nervous system in Goto-Kakizaki diabetic rats

Abstract

　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 high-frequency 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.