Segal S A, Gillis R A
Department of Pharmacology, Georgetown University, School of Medicine, Washington, DC 20007.
Neuropharmacology. 1989 Apr;28(4):367-72. doi: 10.1016/0028-3908(89)90031-2.
The purpose of this study was to determine the site of action in the CNS responsible for producing picrotoxin-induced sympathetic mediated increase in coronary vascular resistance. To do this, picrotoxin, was administered either into the lateral cerebral ventricle, with the perfusion restricted to the forebrain, or into the fourth ventricle, to perfuse only the hindbrain and spinal cord, in chloralose-anesthetized cats, while monitoring coronary blood flow from the anterior descending branch of the left coronary artery, arterial pressure, heart rate and electrocardiogram (ECG). There was no difference between administration into the forebrain and hind-brain in terms of changes in coronary vascular resistance, ECG, arterial pressure and sinus rate when 600 micrograms of picrotoxin was used. Administration into either area elicited significant increases in coronary vascular resistance, arterial pressure and sinus rate, as well as changes in the ST segment and occasional ventricular tachyarrhythmias. However, a separation of effects was noted between the forebrain and the hindbrain when 200 micrograms of picrotoxin was administered. Administration of this dose into the forebrain did not significantly alter coronary vascular resistance or the ST segment, although significant increases in arterial pressure and sinus rate occurred in these animals. In contrast, administration of this dose into the hindbrain elicited significant increases in coronary vascular resistance, ST segment, arterial pressure and sinus rate. These results indicate that the most sensitive site for eliciting picrotoxin-induced increase in coronary vascular lies in the hindbrain.
本研究的目的是确定中枢神经系统中负责产生印防己毒素诱导的交感神经介导的冠状动脉血管阻力增加的作用部位。为此，在氯醛糖麻醉的猫中，将印防己毒素注入侧脑室（灌注仅限于前脑）或第四脑室（仅灌注后脑和脊髓），同时监测左冠状动脉前降支的冠状动脉血流量、动脉压、心率和心电图（ECG）。当使用600微克印防己毒素时，在前脑和后脑给药之间，冠状动脉血管阻力、心电图、动脉压和窦性心率的变化没有差异。向任一区域给药均引起冠状动脉血管阻力、动脉压和窦性心率显著增加，以及ST段改变和偶尔的室性快速心律失常。然而，当给予200微克印防己毒素时，注意到前脑和后脑之间的效应分离。将此剂量注入前脑不会显著改变冠状动脉血管阻力或ST段，尽管这些动物的动脉压和窦性心率显著增加。相比之下，将此剂量注入后脑会引起冠状动脉血管阻力、ST段、动脉压和窦性心率显著增加。这些结果表明，引发印防己毒素诱导的冠状动脉血管增加的最敏感部位位于后脑。
