Fink Anne M, Dean Caron, Piano Mariann R, Carley David W
Center for Narcolepsy, Sleep, and Health Research, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2017 Nov 9;12(11):e0187956. doi: 10.1371/journal.pone.0187956. eCollection 2017.
Elevated renal sympathetic nerve activity (RSNA) accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT) is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH) were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response). Peak increases in RSNA occurred within 10-20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation) from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites), suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to determine whether sympathoexcitatory PPT neurons contribute to adverse renal and cardiovascular consequences of diseases such as obstructive sleep apnea and heart failure.
肾交感神经活动（RSNA）增强伴随着多种复杂疾病，包括阻塞性睡眠呼吸暂停、心力衰竭和慢性肾病。了解病理生理肾机制对于确定高血压为何既是这些疾病的常见后遗症又是诱发因素很重要。脑干在调节RSNA中的作用仍未完全了解。脚桥被盖核（PPT）以调节包括警觉性、运动和快速眼动睡眠等行为而闻名。先前发现，麻醉大鼠中PPT神经元的激活除了改变呼吸外，还会增加内脏交感神经活动和血压。本研究是对PPT及其在调节RSNA中的潜在作用的首次调查。在戊巴比妥麻醉的大鼠中，以100μm的增量微量注射DL-高半胱氨酸（DLH）来探测PPT，以确定有效部位，有效部位定义为可诱发RSNA变化的位置。在18只大鼠中总共进行了239次DLH微量注射，确定了20个有效部位（每个部位均通过诱发可重复的交感兴奋反应的能力得到证实）。RSNA的峰值增加发生在PPT激活后的10 - 20秒内，RSNA从基线增加了104.5±68.4%（平均值±标准差）。平均动脉压在30秒内仍显著升高，从101.6±18.6 mmHg升至135.9±36.4 mmHg。DLH微量注射还增加了呼吸频率和分钟通气量。有效部位遍布PPT的头端-尾端范围，大多数位于核的背侧区域。用DLH微量注射测试的大多数PPT位置并未改变RSNA（179个部位），这表明赋予肾交感兴奋功能的神经元仅占PPT的一小部分。该研究还强调了进一步研究以确定交感兴奋的PPT神经元是否导致诸如阻塞性睡眠呼吸暂停和心力衰竭等疾病的不良肾和心血管后果的重要性。
