Brown S, Chitravanshi V C, Sapru H N
Department of Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Neuroscience. 2006 Dec;143(3):863-74. doi: 10.1016/j.neuroscience.2006.08.026. Epub 2006 Sep 25.
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 i.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-[Nle(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.
据报道，大鼠孤束核（NTS）中存在含促肾上腺皮质激素（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已得到充分证实。基于这些报道，有人推测，在NTS内起作用的ACTH可能会调节心血管功能的中枢调节。为了验证这一假设，在完整的乌拉坦麻醉和未麻醉的去大脑、人工通气的成年雄性Wistar大鼠中，研究了ACTH在NTS中的心血管效应。向NTS内侧亚核（mNTS）微量注射ACTH（0、0.5、1、2和4 mM）可使平均动脉压（MAP）降低（分别为0±0、24.4±3.5、35.7±4.3、44.5±5.8和53.7±5.6 mmHg），心率（HR）降低（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）。对微量注射ACTH（0.5 - 4 mM）的反应的起效时间和持续时间分别为5 - 10秒和45 - 120秒。对照微量注射人工脑脊液（aCSF）未引起任何反应。所有微量注射的体积均为100 nl。当微量注射到mNTS中时能引起降压和心动过缓反应的ACTH浓度（例如1或2 mM，100 nl），静脉注射（n = 5）或脑室内注射（n = 2）时未引起反应，这表明药物没有从mNTS的注射部位泄漏。向mNTS微量注射MC3/4受体拮抗剂（乙酰 - [Nle(4)，Asp(5)，d - 2 - Nal(7)，Lys(10)] - 环 - α - MSH酰胺，片段4 - 10（SHU9119）和刺鼠相关蛋白（83 - 132）酰胺）可阻断对ACTH的反应。向mNTS微量注射ACTH（2 mM）可降低内脏大神经传出活动。双侧迷走神经切断术可显著减弱ACTH诱导的心动过缓。这些结果表明：1）向mNTS微量注射ACTH可引起降压和心动过缓反应；2）这些反应是通过MC3/4受体介导的；3）降压作用是通过交感神经系统活动的降低介导的；4）心动过缓反应是由迷走神经介导的。
