Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Departments of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Pharmacol Rep. 2018 Oct;70(5):1001-1009. doi: 10.1016/j.pharep.2018.03.010. Epub 2018 Apr 4.
The pedunculopontine tegmental (PPT) nucleus is a heterogeneous nucleus with several functions including cardiovascular regulation. The presence of GABA receptor has been shown in the PPT. Therefore, the cardiovascular effects of this receptor were examined.
Rats were divided into: Control; Muscimol; Bicuculline (BMI); Hexamethonium (Hexa)+BMI and Atropine+BMI groups. The femoral vein and artery were cannulated for drug administration and recording of cardiovascular parameters, respectively. Muscimol (a GABA agonist; 1.5 and 2.5nmol), BMI (a GABA antagonist; 0.1 and 0.2nmol) were stereotaxically microinjected into the PPT. To evaluate the peripheral cardiovascular mechanisms of GABA receptors, Hexa (a ganglionic blocker; 10mg/kg) and atropine (a muscarinic receptor antagonist; 1mg/kg) were intravenously (iv) injected before BMI (0.2nmol). The average changes of mean arterial pressure (ΔMAP), systolic blood pressure (ΔSBP) and heart rate (ΔHR) in different intervals were calculated and compared both within and between case group and control group (repeated measures ANOVA). The peak changes in each group were also calculated and compared with those of the control group (independent sample t-test).
Both doses of BMI significantly increased ΔMAP, ΔSBP and ΔHR compared to control, while the only higher dose of muscimol significantly decreased ΔSBP. Iv injection of Hexa significantly attenuated ΔMAP, ΔSBP and ΔHR responses induced by BMI but atropine did not affect.
Our results demonstrate that GABA receptor of the PPT has a tonic inhibitory effect on the cardiovascular system and its peripheral effect mostly is mediated by sympathetic system.
被盖脚桥核(PPT)是一个具有多种功能的核团,包括心血管调节。已经在 PPT 中发现了 GABA 受体的存在。因此,研究了该受体的心血管作用。
将大鼠分为:对照组;Muscimol 组;Bicuculline(BMI)组;Hexamethonium(Hexa)+BMI 组和 Atropine+BMI 组。股静脉和股动脉分别用于给药和记录心血管参数。立体定向微注射 Muscimol(GABA 激动剂;1.5 和 2.5nmol)和 BMI(GABA 拮抗剂;0.1 和 0.2nmol)到 PPT。为了评估 GABA 受体的外周心血管机制,在 BMI(0.2nmol)之前静脉内(iv)注射 Hexa(神经节阻滞剂;10mg/kg)和阿托品(毒蕈碱受体拮抗剂;1mg/kg)。计算不同时间段内平均动脉压(ΔMAP)、收缩压(ΔSBP)和心率(ΔHR)的平均变化,并在病例组和对照组(重复测量方差分析)内和之间进行比较。还计算了每组的峰值变化,并与对照组进行比较(独立样本 t 检验)。
与对照组相比,两种剂量的 BMI 均显著增加了 ΔMAP、ΔSBP 和 ΔHR,而仅较高剂量的 Muscimol 显著降低了 ΔSBP。iv 注射 Hexa 显著减弱了 BMI 引起的 ΔMAP、ΔSBP 和 ΔHR 反应,但阿托品没有影响。
我们的结果表明,PPT 中的 GABA 受体对心血管系统具有紧张性抑制作用,其外周作用主要通过交感神经系统介导。