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A Role for Dopamine in the Centrally Mediated Sympathetic Response in Rats with Type 2 Diabetes Induced by Streptozotocin and a High‐fat Diet
Author(s) -
Zheng Hong,
Liu Xuefei,
Patel Kaushik K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1028.11
Subject(s) - streptozotocin , dopamine , endocrinology , medicine , type 2 diabetes , diabetes mellitus
Dopamine plays an important role in the central nervous system to regulate sympathetic activity and cardiovascular function. The present study was conducted to investigate the role for dopamine in the centrally mediated sympathetic response in rats with type 2 diabetes. To generate a rat model mimicking human type 2 diabetes with increased adiposity, we used a combination of high‐fat diet (HFD, 42% of calories of fat, 3 months) and low‐dose streptozotocin (STZ, 30mg/kg, i.p). In anaesthetized rats, application of dopamine receptor D1/D5 antagonists to the paraventricular nucleus (PVN) of the hypothalamus or rostral ventrolateral medulla (RVLM) results in an increase in heart rate (HR), mean arterial blood (MAP) and renal sympathetic nerve activity (RSNA) in both control and HFD/STZ rats. These responses were significantly attenuated in HFD/STZ rats compared to control rats (ΔHR: 13±7bpm versus 68±16bpm; ΔMAP 6±2mmHg versus 20±3mmHg; ΔRSNA: 11±5% versus 32±9%). There were no significant increases in responses to dopamine receptor D2/D3 antagonist application in either the PVN or the RVLM of both control and HFD/STZ rats. Furthermore we have found decreased dopamine receptor 1 expression (D1DR) in the PVN of HFD/STZ rats. These data suggest that reduced dopaminergic activity in the PVN and RVLM neurons may contribute to the autonomic dysfunction in type 2 diabetes.