Neff Robert A, Wang Jijiang, Baxi Sunit, Evans Cory, Mendelowitz David
Department of Pharmacology, The George Washington University, 2300 Eye St NW, Washington, DC 20037, USA.
Circ Res. 2003 Sep 19;93(6):565-72. doi: 10.1161/01.RES.0000090361.45027.5B. Epub 2003 Aug 7.
The heart rate increases during inspiration and decreases during expiration. This respiratory sinus arrhythmia (RSA) occurs by modulation of premotor cardioinhibitory parasympathetic neuron (CPN) activity. However, RSA has not been fully characterized in rats, and despite the critical role of CPNs in the generation of RSA, little is known about the mechanisms that mediate this cardiorespiratory interaction. This study demonstrates that RSA in conscious rats is similar to that in other species. The mechanism of RSA was then examined in vitro. Rhythmic inspiratory-related activity was recorded from the hypoglossal rootlet of 700- to 800-microm medullary sections. CPNs were identified by retrograde fluorescent labeling, and neurotransmission to CPNs was examined using patch-clamp electrophysiological techniques. During inspiratory bursts, the frequency of both spontaneous gamma-aminobutyric acidergic (GABAergic) and spontaneous glycinergic synaptic events in CPNs was significantly increased. Focal application of the nicotinic antagonist dihydro-beta-erythroidine in an alpha4beta2-selective concentration (3 micromol/L) abolished the respiratory-evoked increase in GABAergic frequency. In contrast, the increase in glycinergic frequency during inspiration was not altered by nicotinic antagonists. Prenatal nicotine exposure exaggerated the increase in GABAergic frequency during inspiration and enhanced GABAergic synaptic amplitude both between and during inspiratory events. Glycinergic synaptic frequency and amplitude were unchanged by prenatal nicotine exposure. This study establishes a neurochemical link between neurons essential for respiration and CPNs, reveals a functional role for endogenous acetylcholine release and the activation of nicotinic receptors in the generation of RSA, and demonstrates that this cardiorespiratory interaction is exaggerated in rats prenatally exposed to nicotine.
吸气时心率增加，呼气时心率降低。这种呼吸性窦性心律不齐（RSA）是通过对运动前心抑制性副交感神经元（CPN）活动的调节而发生的。然而，RSA在大鼠中尚未得到充分表征，尽管CPN在RSA的产生中起着关键作用，但对于介导这种心肺相互作用的机制知之甚少。本研究表明，清醒大鼠的RSA与其他物种相似。然后在体外研究了RSA的机制。从700至800微米延髓切片的舌下神经根记录有节奏的吸气相关活动。通过逆行荧光标记识别CPN，并使用膜片钳电生理技术检查向CPN的神经传递。在吸气爆发期间，CPN中自发性γ-氨基丁酸能（GABA能）和自发性甘氨酸能突触事件的频率均显著增加。以α4β2选择性浓度（3微摩尔/升）局部应用烟碱拮抗剂二氢-β-刺桐碱消除了呼吸诱发的GABA能频率增加。相反，吸气期间甘氨酸能频率的增加不受烟碱拮抗剂的影响。产前尼古丁暴露夸大了吸气期间GABA能频率的增加，并增强了吸气事件之间和期间的GABA能突触幅度。产前尼古丁暴露对甘氨酸能突触频率和幅度没有影响。本研究建立了呼吸必需神经元与CPN之间的神经化学联系，揭示了内源性乙酰胆碱释放和烟碱受体激活在RSA产生中的功能作用，并表明这种心肺相互作用在产前暴露于尼古丁的大鼠中被夸大。
