GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons
GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons
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DOI：
10.1093/cvr/cvq271
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发表时间：
2011-01-01
影响因子：
10.8
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
--
作者：
Griffioen, Kathleen J.;Wan, Ruiqian;Mattson, Mark P.
胰高血糖素样肽 1 (GLP-1) 是一种肠促胰岛素激素，响应食物摄入而从肠道释放。 GLP-1 在外周发挥作用，抑制胰高血糖素分泌并刺激胰岛素释放，它也在中枢神经系统中发挥作用，介导进食、体温和心血管功能的自主控制。由于其作为肠促胰岛素激素的作用，GLP-1 受体类似物被用来治疗 2 型糖尿病。中枢或外周给药 GLP-1 可能会通过激活脑干自主神经核和增加迷走神经活动来增加血压和心率。然而，GLP-1 受体刺激影响心血管功能的机制尚不清楚。我们使用长效 GLP-1 受体激动剂 Exendin-4 (Ex-4) 来检验 GLP-1 信号传导调节中枢副交感神经控制心率的假设。方法和结果 使用遥测系统，我们评估了中枢 Ex-4 给药期间小鼠的心率。急性和慢性中枢Ex-4给药都会增加心率。频谱分析表明，Ex-4 治疗降低了心率变异性的高频和低频功率。最后，Ex-4 减少了向节前副交感心脏迷走神经元的兴奋性谷氨酸能和抑制性甘氨酸能神经传递。结论这些数据表明，中枢GLP-1 受体刺激减少了心脏的副交感神经调节，从而增加了心率。
Aims Glucagon-like peptide 1 (GLP-1) is an incretin hormone released from the gut in response to food intake. Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function. Because of its role as an incretin hormone, GLP-1 receptor analogs are used as a treatment for type 2 diabetes. Central or peripheral administration of GLP-1 increases blood pressure and heart rate, possibly by activating brainstem autonomic nuclei and increasing vagus nerve activity. However, the mechanism(s) by which GLP-1 receptor stimulation affects cardiovascular function are unknown. We used the long-lasting GLP-1 receptor agonist Exendin-4 (Ex-4) to test the hypothesis that GLP-1 signalling modulates central parasympathetic control of heart rate.Methods and results Using a telemetry system, we assessed heart rate in mice during central Ex-4 administration. Heart rate was increased by both acute and chronic central Ex-4 administration. Spectral analysis indicated that the high frequency and low frequency powers of heart rate variability were diminished by Ex-4 treatment. Finally, Ex-4 decreased both excitatory glutamatergic and inhibitory glycinergic neurotransmission to preganglionic parasympathetic cardiac vagal neurons.Conclusion These data suggest that central GLP-1 receptor stimulation diminishes parasympathetic modulation of the heart thereby increasing heart rate.