Hildreth Cara M, Padley James R, Pilowsky Paul M, Goodchild Ann K
Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H474-80. doi: 10.1152/ajpheart.01009.2007. Epub 2007 Nov 9.
Serotonin (5-HT) is crucial to normal reflex vagal modulation of heart rate (HR). Reduced baroreflex sensitivity [spontaneous baroreflex sensitivity (sBRS)] and HR variability (HRV) reflect impaired neural, particularly vagal, control of HR and are independently associated with depression. In conscious, telemetered Flinders-Sensitive Line (FSL) rats, a well-validated animal model of depression, we tested the hypothesis that cardiovascular regulatory abnormalities are present and associated with deficient serotonergic control of reflex cardiovagal function. In FSL rats and control Flinders-Resistant (FRL) and Sprague-Dawley (SD) rat strains, diurnal measurements of HR, arterial pressure (AP), activity, sBRS, and HRV were made. All strains had normal and similar diurnal variations in HR, AP, and activity. In FRL rats, HR was elevated, contributing to the reduced HRV and sBRS in this strain. In FSL rats, sBRS and high-frequency power HRV were reduced during the night, indicating reduced reflex cardiovagal activity. The ratio of low- to high-frequency bands of HRV was increased in FSL rats, suggesting a relative predominance of cardiac sympathetic and/or reflex activity compared with FRL and SD rats. These data show that conscious FSL rats have cardiovascular regulatory abnormalities similar to depressed humans. Acute changes in HR, AP, temperature, and sBRS in response to 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A), 5-HT(1B), and 5-HT(7) receptor agonist, were also determined. In FSL rats, despite inducing an exaggerated hypothermic effect, 8-hydroxy-2-(di-n-propylamino)tetralin did not decrease HR and AP or improve sBRS, suggesting impaired serotonergic neural control of cardiovagal activity. These data suggest that impaired serotonergic control of cardiac reflex function could be one mechanism linking reduced sBRS to increased cardiac risk in depression.
血清素（5-羟色胺，5-HT）对于心率（HR）的正常反射性迷走神经调节至关重要。压力反射敏感性降低[自发性压力反射敏感性（sBRS）]和心率变异性（HRV）反映了神经对心率控制的受损，尤其是迷走神经，并且与抑郁症独立相关。在清醒的、可遥测的弗林德斯敏感品系（FSL）大鼠中，这是一种经过充分验证的抑郁症动物模型，我们测试了以下假设：心血管调节异常存在且与反射性心迷走功能的血清素能控制不足有关。在FSL大鼠以及对照的弗林德斯抗性（FRL）和斯普拉格-道利（SD）大鼠品系中，对心率、动脉压（AP）、活动、sBRS和HRV进行了昼夜测量。所有品系在心率、动脉压和活动方面都有正常且相似的昼夜变化。在FRL大鼠中，心率升高，导致该品系的HRV和sBRS降低。在FSL大鼠中，夜间sBRS和高频功率HRV降低，表明反射性心迷走活动减少。FSL大鼠中HRV的低频与高频波段比值增加，表明与FRL和SD大鼠相比，心脏交感神经和/或反射活动相对占优势。这些数据表明，清醒的FSL大鼠具有与抑郁症患者相似的心血管调节异常。还测定了对5-HT（1A）、5-HT（1B）和5-HT（7）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘的反应中HR、AP、温度和sBRS的急性变化。在FSL大鼠中，尽管8-羟基-2-（二正丙基氨基）四氢萘诱导了夸张的低温效应，但它并没有降低心率和动脉压，也没有改善sBRS，这表明血清素能神经对心迷走活动的控制受损。这些数据表明，血清素能对心脏反射功能的控制受损可能是将sBRS降低与抑郁症中心脏风险增加联系起来的一种机制。
