Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats
Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats
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DOI：
10.1152/ajpregu.00392.2011
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发表时间：
2012-03-01
影响因子：
2.8
通讯作者：
Hall, John E.
中科院分区：
文献类型：
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作者：
do Carmo, Jussara M.;da Silva, Alexandre A.;Hall, John E.
卡尔莫 JM、达席尔瓦 AA、拉欣 JS、霍尔 JE。中枢黑皮质素系统的激活导致肥胖 Zucker 大鼠动脉压升高。 Am J Physiol Regul Integr Comp Physiol 302：R561-R567，2012。首次发表于 2011 年 12 月 28 日； doi:10.1152/ajpregu.00392.2011.-我们之前已经证明瘦素介导的中枢神经系统 (CNS) 黑皮质素系统的激活会降低食欲并增加交感神经活动和血压 (BP)。在本研究中，我们检查了内源性黑皮质素系统的激活（与瘦素的作用无关）是否有助于肥胖 Zucker 大鼠（瘦素受体突变）的血压和代谢功能的调节。在瘦（n = 6）和肥胖（n = 8）Zucker 大鼠中评估了 SHU-9119 拮抗中枢黑皮质素-3/4 受体 (MC3/4R) 的长期心血管和代谢影响。通过遥测技术每天 24 小时测量血压和心率 (HR)，并将脑室内插管放置在大脑侧脑室中。控制测量稳定后，将 SHU-9119 脑室内输注（1 nmol/h）10 天，然后是 10 天的恢复期。慢性CNS MC3/4R拮抗作用显着增加瘦大鼠（20+/-1至45+/-2g和373+/-11至432+/-14g）和肥胖大鼠（25+/-2至35+/-2g和547+/-10至604+/-11g）的食物摄入量和体重。在 CNS MC3/4R 拮抗作用期间，瘦或肥胖大鼠的血浆葡萄糖水平没有观察到显着变化，而瘦 Zucker 大鼠的血浆瘦素和胰岛素水平显着增加。肥胖 Zucker 大鼠的长期 SHU-9119 输注使平均动脉压 (MAP) 和 HR 降低 6 +/- 1 mmHg 和 24 +/- 5 次/分钟，而在瘦大鼠中，SHU-9119 输注使 HR 降低 31 +/- 9 次/分钟，同时仅导致 MAP 短暂降低。这些结果表明，在肥胖 Zucker 大鼠中，中枢神经系统黑皮质素系统导致血压升高，与瘦素受体激活无关。
do Carmo JM, da Silva AA, Rushing JS, Hall JE. Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 302: R561-R567, 2012. First published December 28, 2011; doi:10.1152/ajpregu.00392.2011.-We have previously demonstrated that leptin-mediated activation of the central nervous system (CNS) melanocortin system reduces appetite and increases sympathetic activity and blood pressure (BP). In the present study we examined whether endogenous melanocortin system activation, independent of leptin's actions, contributes to the regulation of BP and metabolic functions in obese Zucker rats, which have mutated leptin receptors. The long-term cardiovascular and metabolic effects of central melanocortin-3/4 receptor (MC3/4R) antagonism with SHU-9119 were assessed in lean (n = 6) and obese (n = 8) Zucker rats. BP and heart rate (HR) were measured 24-h/day by telemetry and an intracerebroventricular cannula was placed in the brain lateral ventricle. After stable control measurements, SHU-9119 was infused intracerebroventricularlly (1 nmol/h) for 10 days followed by a 10-day recovery period. Chronic CNS MC3/4R antagonism significantly increased food intake and body weight in lean (20 +/- 1 to 45 +/- 2 g and 373 +/- 11 to 432 +/- 14 g) and obese (25 +/- 2 to 35 +/- 2 g and 547 +/- 10 to 604 +/- 11 g) rats. No significant changes were observed in plasma glucose levels in lean or obese rats, whereas plasma leptin and insulin levels markedly increased in lean Zucker rats during CNS MC3/4R antagonism. Chronic SHU-9119 infusion in obese Zucker rats reduced mean arterial pressure (MAP) and HR by 6 +/- 1 mmHg and 24 +/- 5 beats/min, whereas in lean rats SHU-9119 infusion reduced HR by 31 +/- 9 beats/min while causing only a transient decrease in MAP. These results suggest that in obese Zucker rats the CNS melanocortin system contributes to elevated BP independent of leptin receptor activation.