Attenuated dopaminergic tone in the paraventricular nucleus contributing to sympathoexcitation in rats with Type 2 diabetes

作者：Zheng Hong^*; Liu Xuefei; Li Yulong; Mishra Paras K; Patel Kaushik P

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2014, 306(2): R138-R148.

DOI：10.1152/ajpregu.00323.2013

• central nervous system
• dopaminergic
• sympathetic nerve activity

The study was conducted to investigate the role for dopamine in the centrally mediated sympathoexcitatory response in rats with Type 2 diabetes (T2D). T2D was induced by a combination of high-fat diet (HFD) and low-dose streptozotocin (STZ). HFD/STZ treatment for 12-14 wk resulted in significant increase in the number of FosB-positive cells in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM). In anesthetized rats, administration of exogenous dopamine (dopamine hydrochloride, 20 mM) in the PVN, but not in the RVLM, elicited decreases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in control rats and but not in the T2D rats. Blocking the endogenous dopamine with dopamine D-1/D-5 receptor antagonist SCH39166 (2 mM) in the PVN and RVLM, resulted in increases in RSNA, MAP, and heart rate (HR) in both control and T2D rats. These responses were significantly attenuated in T2D rats compared with control rats (PVN RSNA: 21 +/- 10 vs. 44 +/- 2%; Delta MAP: 7 +/- 3 vs. 19 +/- 6 mmHg, HR: 17 +/- 5 vs. 32 +/- 4 bpm, P %26lt; 0.05). There were no significant increases in response to dopamine D-2/D-3 receptor antagonist raclopride application in the PVN and RVLM of both control and T2D rats. Furthermore, there were decreased dopamine D-1 receptor and D-2 receptor expressions in the PVN of T2D rats. Taken together, these data suggest that reduced endogenous dopaminergic tone within the PVN may contribute to the sympathoexcitation in T2D.

• 出版日期2014-1