Key result
Streptozotocin-induced diabetes in rats drives severe cardiac parasympathetic damage and sympathetic nerve remodeling.
Why the study?
Diabetes mellitus is associated with cardiovascular and autonomic nervous system dysfunction, but detailed analysis of cardiac autonomic nerve remodeling in diabetes is lacking.
In a rat model, STZ-induced diabetes leads to significant cardiac autonomic nerve dysfunction characterized by early parasympathetic damage and subsequent sympathetic remodeling.
No immediate clinical implications from rat data; leaves open whether similar remodeling drives human diabetic autonomic neuropathy.
BACKGROUND: Diabetes mellitus (DM) is associated with both cardiovascular and autonomic nervous system dysfunction. Spectral analysis of heart rate variability (HRV) can be used to monitor changes in response to autonomic innervation and stimulation of the heart. In this study, conducted in a rat model of diabetes, HRV and changes in associated neurotransmitters and neurotrophic factors in the right atrium (RA) were monitored. METHODS: Diabetes was induced by streptozotocin (STZ) (60 mg/kg) in male Wistar rats, and HRV data were collected for 10 weeks by telemetry. Time and frequency domains of HRV data were analyzed using established metrics. The levels of various neural enzymes in the RA were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence to characterize autonomic nerve remodeling. Insulin and methycobal were used to block the effects of STZ. RESULTS: HRV parameters reflecting parasympathetic tone (SDNN, RMSSD and HF domains) sharply decreased in the first 3 weeks after STZ administration; measures of sympathetic tone (SDANN) increased. After a series of adjustments, cardiac autonomic nerve innervation reached a new equilibrium, with a dominance of sympathetic tone. RA levels of tyrosine hydroxylase (TH) increased, and choline acetyltransferase (ChAT) decreased, indicating autonomic nerve remodeling. Levels of growth associated protein-43 (GAP43) and nerve growth factor (NGF) increased during the period of diabetes-induced cardiac-nerve damage; however, the level of ciliary neurotrophic factor (CNTF) decreased. The physical condition and indexes of rats were normalized in different degree after administration of the insulin and methycobal, but not completely recovered. CONCLUSION: STZ-induced diabetes was associated with cardiac autonomic nerve dysfunction at both the organ and molecular levels. Parasympathetic nerves exhibited severe damage and/or weak recovery; remodeling of sympathetic nerves predominated during 10-weeks of STZ-induced diabetes.
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Li et al. (2015) studied Diabetes mellitus. Streptozotocin (STZ) was evaluated on Heart rate variability (HRV) and cardiac autonomic nerve remodeling. Streptozotocin-induced diabetes in rats caused severe parasympathetic nerve damage and predominant sympathetic nerve remodeling over 10 weeks.
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