Segal S A, Jacob T, Gillis R A
Circ Res. 1984 Sep;55(3):404-15. doi: 10.1161/01.res.55.3.404.
Picrotoxin, an antagonist of gamma-aminobutyric acid, produces an increase in coronary vascular resistance, S-T segment elevation, and ventricular arrhythmias after an intravenous injection of 2 mg/kg in chloralose-anesthetized cats. To determine whether these responses were due to blockade of central nervous system GABAergic mechanisms leading to an increase in sympathetic outflow to the coronary vasculature, several types of experiments were performed. First, picrotoxin was injected directly into the brain in a dose of 600 micrograms while coronary blood flow and S-T segment changes were monitored. Central nervous system administration of this agent resulted in a significant increase in coronary vascular resistance, S-T segment elevation, and arrhythmias. Second, animals were pretreated with the gamma-aminobutyric acid receptor agonist drug, muscimol, prior to central administration of picrotoxin. Pretreatment prevented the usual increase in coronary vascular resistance, S-T segment elevation, and arrhythmias. Third, animals were subjected to acute bilateral cardiac sympathetic denervation prior to picrotoxin administration. Denervation attenuated the picrotoxin-induced increase in coronary vascular resistance (mean = 11.6 +/- 2.1% vs. 26.1 +/- 7.1%, P less than 0.05) and elevation in S-T segment (mean = 0.09 +/- 0.03 mV vs. 0.29 +/- 0.04 mV, P less than 0.05), and prevented arrhythmias. Pretreatment with the alpha-receptor blocking agent, phentolamine, produced even more pronounced antagonistic effects. These results suggest that blockade of central nervous system GABAergic tone leads to enhanced sympathetic outflow to the coronary vasculature, resulting in an increase in coronary vascular resistance of sufficient intensity to cause S-T segment elevation and arrhythmias.
印防己毒素是γ-氨基丁酸的拮抗剂，在给氯醛糖麻醉的猫静脉注射2mg/kg后，可使冠状动脉血管阻力增加、S-T段抬高并出现室性心律失常。为了确定这些反应是否是由于中枢神经系统γ-氨基丁酸能机制被阻断，导致交感神经向冠状动脉血管的输出增加，进行了几种类型的实验。首先，在监测冠状动脉血流量和S-T段变化的同时，以600微克的剂量将印防己毒素直接注入脑内。向中枢神经系统给予这种药物导致冠状动脉血管阻力显著增加、S-T段抬高和心律失常。其次，在向中枢给予印防己毒素之前，先用γ-氨基丁酸受体激动剂药物蝇蕈醇对动物进行预处理。预处理可防止冠状动脉血管阻力、S-T段抬高和心律失常的通常增加。第三，在给予印防己毒素之前，对动物进行急性双侧心脏交感神经去神经支配。去神经支配减弱了印防己毒素引起的冠状动脉血管阻力增加（平均值分别为11.6±2.1%和26.1±7.1%，P<0.05）和S-T段抬高（平均值分别为0.09±0.03mV和0.29±0.04mV，P<0.05），并预防了心律失常。用α受体阻断剂酚妥拉明进行预处理产生了更明显的拮抗作用。这些结果表明，中枢神经系统γ-氨基丁酸能张力的阻断导致交感神经向冠状动脉血管的输出增强，从而导致冠状动脉血管阻力增加到足以引起S-T段抬高和心律失常的强度。
