Key result
Blocking endogenous dopamine with SCH39166 in the PVN resulted in significantly attenuated increases in RSNA, MAP, and HR in T2D rats compared with control rats (P < 0.05).
p-value: p=< 0.05
Reduced endogenous dopaminergic tone within the paraventricular nucleus may contribute to sympathoexcitation in Type 2 diabetes.
May implicate PVN dopamine loss in T2D sympathoexcitation; hypothesis-generating from animal data, needs human confirmation.
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 D1/D5 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 - ΔRSNA: 21 ± 10 vs. 44 ± 2%; ΔMAP: 7 ± 3 vs. 19 ± 6 mmHg, ΔHR: 17 ± 5 vs. 32 ± 4 bpm, P < 0.05). There were no significant increases in response to dopamine D2/D3 receptor antagonist raclopride application in the PVN and RVLM of both control and T2D rats. Furthermore, there were decreased dopamine D1 receptor and D2 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.
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Zheng et al. (2013) studied Type 2 diabetes. Dopamine D1/D5 receptor antagonist SCH39166 vs. Control rats was evaluated on Changes in renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in response to SCH39166 in the PVN (p=< 0.05). Blocking endogenous dopamine with SCH39166 in the PVN resulted in significantly attenuated increases in RSNA, MAP, and HR in T2D rats compared with control rats (P < 0.05).
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