Cardiovascular actions of adrenocorticotropin microinjections into the nucleus tractus solitarius of the rat
Cardiovascular actions of adrenocorticotropin microinjections into the nucleus tractus solitarius of the rat
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DOI：
10.1016/j.neuroscience.2006.08.026
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发表时间：
2006-12-13
期刊：
影响因子：
3.3
通讯作者：
Sapru, H. N.
中科院分区：
文献类型：
--
作者：
Brown, S.;Chitravanshi, V. C.;Sapru, H. N.
据报道，在大鼠的孤束核（NTS）中存在含有促肾上腺皮质激素（ACTH）的细胞和黑皮质素（MC）受体。 NTS 在心血管功能调节中的重要性也是众所周知的。基于这些报告，推测在 NTS 内作用的 ACTH 可能调节心血管功能的中枢调节。为了验证这一假设，我们在完整的氨基甲酸乙酯麻醉和未麻醉的去脑、人工通气的成年雄性 Wistar 大鼠中研究了 NTS 中 ACTH 的心血管效应。将 ACTH（0、0.5、1、2 和 4 mM）显微注射到 NTS（mNTS）内侧亚核中会引起平均动脉压降低（MAP；分别为 0 +/- 0、24.4 +/- 3.5、35.7 +/- 4.3、44.5 +/- 5.8 和 53.7 +/- 5.6 mm Hg）和心率（HR；分别为 0 +/- 0、25.7 +/- 5.3、35.5 +/- 6.4、47.5 +/- 12.1 和 55.0 +/- 5.6 次/分钟）。对显微注射 ACTH (0.5-4 mM) 的反应的起始时间和持续时间分别为 5-10 秒和 45-120 秒。人工脑脊液（aCSF）的对照显微注射没有引起任何反应。所有显微注射的体积为100 nl。当显微注射到 mNTS 中时引起抑制和心动过缓反应的 ACTH 浓度（例如 1 或 2 mM，100 nl），当静脉注射时不会引起反应。 (n=5) 或 l.c.v. (n=2)表明mNTS中的注射部位没有药物泄漏。将 MC3/4 受体拮抗剂（乙酰基-[Nie(4)、Asp(5)、D-2-Nal(7)、Lys(10)]-cyclo-alpha-MSH 酰胺、片段 4-10 (SHU9119) 和刺鼠相关蛋白 (83-132) 酰胺）显微注射到 mNTS 中，可阻断对 ACTH 的反应。将 ACTH (2 mM) 显微注射到 mNTS 中可减少内脏传出神经活动。双侧迷走神经切断术显着减弱 ACTH 引起的心动过缓。这些结果表明：1) 将 ACTH 显微注射到 mNTS 中会引发抑制反应和心动过缓反应，2) 这些反应是通过 MC3/4 受体介导的，3) 抑制作用是通过交感神经系统活性的降低介导的，4) 心动过缓反应是迷走神经介导的。 (c) 2006 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
The presence of adrenocorticotropin (ACTH) containing cells and melanocortin (MC) receptors has been reported in the nucleus tractus solitarius (NTS) of the rat. The importance of the NTS in the regulation of cardiovascular function is also well established. Based on these reports, it was hypothesized that ACTH acting within the NTS may modulate the central regulation of cardiovascular function. To test this hypothesis, cardiovascular effects of ACTH in the NTS were investigated in intact urethane-anesthetized and unanesthetized decerebrate, artificially ventilated, adult male Wistar rats. Microinjections of ACTH (0, 0.5, 1, 2, and 4 mM) into the medial subnucleus of NTS (mNTS) elicited decreases in mean arterial pressure (MAP; 0 +/- 0, 24.4 +/- 3.5, 35.7 +/- 4.3, 44.5 +/- 5.8 and 53.7 +/- 5.6 mm Hg, respectively) and heart rate (HR; 0 +/- 0, 25.7 +/- 5.3, 35.5 +/- 6.4, 47.5 +/- 12.1 and 55.0 +/- 5.6 beats/min, respectively). The onset and duration of the responses to microinjections of ACTH (0.5-4 mM) were 5-10 s and 45-120 s, respectively. Control microinjections of artificial cerebrospinal fluid (aCSF) did not elicit any response. The volume of all microinjections was 100 nl. The concentrations of ACTH that elicited depressor and bradycardic responses when microinjected into the mNTS (e.g. 1 or 2 mM, 100 nl), did not elicit a response when injected i.v. (n=5) or l.c.v. (n=2) indicating that there was no leakage of the drug from the injection site in the mNTS. Microinjections of MC3/4 receptor antagonists (acetyl-[Nie(4), Asp(5), D-2-Nal(7), Lys(10)]-cyclo-alpha-MSH amide, fragments 4-10 (SHU9119) and agouti-related protein (83-132) amide) into the mNTS blocked the responses to ACTH. Microinjections of ACTH (2 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Bilateral vagotomy significantly attenuated ACTH-induced bradycardia. These results indicated that: 1) microinjections of ACTH into the mNTS elicited depressor and bradycardic responses, 2) these responses were mediated via MC3/4 receptors, 3) the depressor effects were mediated via a decrease in the activity of the sympathetic nervous system, and 4) the bradycardic responses were vagally mediated. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.