Wible J H, DiMicco J A
Brain Res. 1986 Jan 22;363(2):279-89. doi: 10.1016/0006-8993(86)91013-9.
Systemic administration of the GABA antagonist picrotoxin 6.0 mg/kg i.v. elicited hypertension and a fall in sinus rate with a return to baseline levels in intact rats. Antagonists of GABA act in the supraspinal CNS to augment sympathetic outflow to the heart and vasculature. Therefore, in this study the spinal cord was transected prior to drug administration in order to eliminate sympathetically mediated effects. In spinal rats, picrotoxin 6.0 mg/kg evoked a biphasic sinus rate response characterized by an initial decrease followed by an increase above baseline sinus rate. Bilateral vagotomy or atropine pretreatment blocked sinus rate changes elicited by picrotoxin, demonstrating that these effects were vagally mediated. Midcollicular decerebration altered the biphasic sinus rate response by preventing the late rise but not the initial decrease in sinus rate. Infusion of another GABA antagonist, bicuculline, elicited a similar biphasic sinus rate response, although the time-course was shorter. Unexpectedly, picrotoxin or bicuculline administration in spinal rats caused an increase in mean blood pressure which was prevented by decerebration and different from that observed in intact rats with respect to time course. In spinal rats pretreatment with a vasopressin antagonist, D(CH2)5Tyr(Me)AVP, blocked the pressor response induced by picrotoxin infusion without altering the biphasic changes in sinus rate. These results suggest that, in the rat: (1) two GABAergic inhibitory mechanisms at different levels of the neuraxis exert opposite effects on cardiac vagal activity; and (2) GABA antagonists may elevate arterial pressure by a mechanism distinct from their previously described sympathoexcitatory effects.
静脉注射6.0毫克/千克的GABA拮抗剂印防己毒素可使完整大鼠出现高血压和窦性心率下降，随后恢复至基线水平。GABA拮抗剂作用于脊髓上的中枢神经系统，增强对心脏和血管系统的交感神经输出。因此，在本研究中，在给药前切断脊髓以消除交感神经介导的效应。在脊髓大鼠中，6.0毫克/千克的印防己毒素引起双相性窦性心率反应，其特征是最初下降，随后高于基线窦性心率水平上升。双侧迷走神经切断术或阿托品预处理可阻断印防己毒素引起的窦性心率变化，表明这些效应是由迷走神经介导的。中脑桥脑断离改变了双相性窦性心率反应，阻止了窦性心率的后期上升，但未阻止其最初下降。输注另一种GABA拮抗剂荷包牡丹碱也引起了类似的双相性窦性心率反应，尽管时程较短。出乎意料的是，在脊髓大鼠中给予印防己毒素或荷包牡丹碱会导致平均血压升高，脑桥脑断离可阻止这种升高，且在时程方面与在完整大鼠中观察到的不同。在脊髓大鼠中，用血管加压素拮抗剂D(CH2)5Tyr(Me)AVP预处理可阻断印防己毒素输注诱导的升压反应，而不改变窦性心率的双相变化。这些结果表明，在大鼠中：(1)神经轴不同水平的两种GABA能抑制机制对心脏迷走神经活动产生相反的影响；(2)GABA拮抗剂可能通过一种不同于其先前描述的交感神经兴奋作用的机制升高动脉血压。
