Dipartimento di Biologia Evolutiva e Funzionale, Universitàdi Parma, Parma, Italy.
Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R1123-31. doi: 10.1152/ajpregu.00273.2011. Epub 2011 Jul 27.
In humans, chronic stressors have long been recognized as potential causes for cardiac dysregulation. Despite this, the underlying mechanistic links responsible for this association are still poorly understood. The purpose of this study was to determine whether exposure to a paradigm of subchronic stress can provoke enduring changes on the heart rate of experimental rats and, if so, to reveal the autonomic and neural mechanisms that mediate these effects. The study was conducted on adult male Sprague-Dawley rats instrumented for telemetric recording of heart rate and locomotor activity. Animals were submitted to a subchronic stress protocol, consisting of a 1-h foot shock session on five consecutive days. Heart rate and locomotor activity were recorded continuously for 3 days before and for 6 days after the subchronic stress period. Subchronic foot shock produced significant and enduring reduction in heart rate both during the dark/active [Δ= -23 ± 3 beats per minute (bpm)] and light/inactive (Δ= -20 ± 3 bpm) phases of the circadian cycle, and a reduction in locomotor activity during the dark/active phase [Δ= -54 ± 6 counts per hour (cph)]. The bradycardic effect of subchronic stress was not related to a reduced locomotion. Selective sympathetic (atenolol) and vagal (methyl-scopolamine) blockades were performed to reveal which autonomic component was responsible for this effect. We found that the fall in heart rate persisted after subchronic stress in animals treated with atenolol (active phase Δ= -16 ± 3 bpm, inactive phase Δ= -19 ± 2 bpm), whereas vagal blockade with scopolamine transiently prevented this effect, suggesting that the bradycardia following subchronic stress was predominantly vagally mediated. Fluoxetine (selective serotonin reuptake inhibitor) and metyrapone (inhibitor of corticosterone synthesis) treatments did not affect heart rate changes but prevented the reduction in locomotion. We conclude that subchronic stress exposure in rats reduces heart rate via a rebound in vagal activation and that this effect is serotonin- and corticosterone-independent.
在人类中，长期以来一直认为慢性应激源是心脏调节失常的潜在原因。尽管如此，导致这种关联的潜在机制联系仍知之甚少。本研究的目的是确定暴露于亚慢性应激范式是否会引起实验大鼠心率的持久变化，如果是这样，那么揭示介导这些效应的自主和神经机制。该研究是在接受遥测记录心率和运动活动仪器的成年雄性 Sprague-Dawley 大鼠上进行的。动物接受亚慢性应激方案，包括连续五天每天进行 1 小时的足底电击。在亚慢性应激期之前和之后连续 3 天记录心率和运动活动。亚慢性足底电击会导致心率明显且持久的降低，无论是在昼夜节律周期的暗/活跃[Δ= -23 ± 3 次/分钟（bpm）]和亮/不活跃[Δ= -20 ± 3 bpm]阶段，还是在暗/活跃阶段运动活动减少[Δ= -54 ± 6 次/小时（cph）]。亚慢性应激的心动过缓效应与运动减少无关。进行选择性交感（阿替洛尔）和迷走神经（甲基东莨菪碱）阻断以揭示哪个自主成分是造成这种效应的原因。我们发现，在接受阿替洛尔治疗的动物中，亚慢性应激后的心率下降持续存在（活跃期 Δ= -16 ± 3 bpm，不活跃期 Δ= -19 ± 2 bpm），而用东莨菪碱进行迷走神经阻断则暂时阻止了这种效应，表明亚慢性应激后出现的心动过缓主要是迷走神经介导的。氟西汀（选择性 5-羟色胺再摄取抑制剂）和甲吡酮（皮质酮合成抑制剂）治疗不会影响心率变化，但会防止运动减少。我们的结论是，大鼠暴露于亚慢性应激会通过迷走神经激活的反弹而降低心率，而这种效应与 5-羟色胺和皮质酮无关。
