Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Auton Neurosci. 2010 Jun 24;155(1-2):39-48. doi: 10.1016/j.autneu.2010.01.004. Epub 2010 Feb 20.
Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state DeltaHR/DeltaMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.
心率（HR）的压力反射控制在人类糖尿病和大型实验模型中受损。然而，糖尿病小鼠模型中的压力反射损伤以及糖尿病引起的压力反射回路重塑尚未得到很好的研究。我们检查了链脲佐菌素（STZ）诱导的糖尿病小鼠模型中 HR 的压力反射控制受损情况，并评估了心脏神经节的结构重塑。FVB 小鼠要么注射载体，要么注射 STZ。第 1 组：小鼠麻醉，在注射载体或 STZ 后的第 30 天经股动脉和股静脉插管。手术后第二天，在清醒小鼠中测量硝普钠（SNP）和苯肾上腺素（PE）诱导的平均动脉血压（MABP）变化对压力反射介导的 HR 反应。第 2 组：在注射载体或 STZ 后的第 25 天，通过腹腔注射 Fluoro-Gold 标记每个小鼠的心脏神经节。五天后，动物进行灌注，使用共聚焦显微镜检查心脏神经节。与对照组相比，我们在 STZ 小鼠中发现：1）HR 降低，但 MABP 没有。2）PE 诱导的 MABP 增加减少。3）在快速 MABP 上升阶段，压力反射性心动过缓减弱，但在所有 PE 剂量下稳态 DeltaHR/DeltaMABP 没有差异。4）SNP 诱导的 MABP 降低没有差异。5）压力反射性心动过速减弱。6）心脏神经节和神经节主神经元的大小减小。7）心脏神经节神经元核/细胞体的比例增加。我们得出结论，在清醒的 STZ 小鼠中，HR 的压力反射控制受损。此外，糖尿病可能会引起心脏神经节的显著结构重塑。这种心脏神经节的解剖结构变化可能为理解糖尿病引起的压力反射回路中多个成分的重塑提供新的信息。
