Carvedilol improves heart rate variability indices, biomarkers but not cardiac nerve density in streptozotocin-induced T2DM model of diabetic cardiac autonomic neuropathy

Abstract

Abstract Objectives There has been increasing recognition of the significant relationship between the autonomic nervous system and cardiovascular sequel in diabetes mellitus (DM) patients. Diabetic cardiac autonomic neuropathy (DCAN) still poses a treatment challenge in the clinical settings despite several research interventions. This study was designed to investigate the effect of carvedilol on experimentally induced DCAN in type 2 DM rat model. Methods DCAN was induced in 42 Wistar rats using high fat diet (HFD) for eight weeks, thereafter streptozotocin (STZ) at 25 mg/kg daily for five days. DCAN features were then assessed using non-invasive time and frequency varying holter electrocardiogram (ECG), invasive biomarkers, cardiac histology and cardiac nerve density. Results Carvedilol significantly ameliorated the effects of DCAN on noradrenaline (p=0.010) and advanced glycated end products (AGEs) (p<0.0001). Similarly, carvedilol reversed the reduction in levels of antioxidants, sorbitol dehydrogenase (SD) activity (p=0.009) nerve growth factors (p<0.0001) and choline acetyl-transferase (p=0.031) following DCAN induction. Furthermore, heart rate variability (HRV) indices which were also reduced with DCAN induction were also ameliorated by carvedilol. However, carvedilol had no significant effect on cardiac neuronal dystrophy and reduced cardiac nerve densities. Conclusions Carvedilol improves physiological HRV indices and biomarkers but not structural lesions. Early detection of DCAN and intervention with carvedilol may prevent progression of autonomic neurologic sequel.