安定降低家兔血压和减少刺激下丘脑诱发室性期前收缩的机制分析

家兔62只,用乌拉坦(700mg/kg)和氯醛醣(35mg/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。用电刺激下丘脑近中线区的方法诱发室性期前收缩(HVE)。静脉注射安定(0.5mg/kg)可降低基础血压(BP),减弱刺激下丘脑引起升压反应(指收缩压峰值SBP_(max))和减少HVE。在双侧延髓腹外侧头端区(rVLM)微量注射氟安定(200μg溶于0.5μl中),γ-氨基丁酸(GABA)(6μg溶于0.5μl中)均能降低BP、SBP_(max)和减少HVE,若微量注射印防己毒素(7.5μg溶于0.5μl中)则可使BP上升并增多HVE。而于双侧延髓腹外侧尾端区(cVLM)微量注射同样剂量氟安定、GABA则无上述反应。安定降低BP、SBP_(max)和减少HVE的作用可被双侧rVLM区微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl中)或印防己毒素所消除,但在双侧rVLM区微量注射甘氨酸受体拮抗剂士的宁(1μg溶于0.5μl中)、阿片受体拮抗剂纳洛酮(0.5μg溶于0.5μl中)、胆碱能阻断药阿托品(0.25μg溶于0.5μl中)、东莨菪碱(1.5μg溶于0.5μl中)后仍然存在。 上述结果提示,在双侧rVLM应用GABA受体拮抗剂可消除安定降低BP、SBP_(max)和减少HVE的作用,安定降低BP、SBP_(max)和减少HVE的作用可能通过GABA这一中间环节,而胆碱能受体、阿片受体、甘氨酸受体可能不起重要作用。

MECHANISM OF DEPRESSING EFFECT OF DIAZEPAM ON THE BLOOD PRESSURE AND ON VENTRICULAR EXTRASYSTOLES INDUCED BY HYPOTHALAMIC STIMULATION IN THE RABBIT

Experiments were carried out on 62 rabbits anesthetized with urethane and chloralose and immobilized with gallamine triethiodide under artificial ventilation. Ventricular extrasystoles were induced by electrical stimulation of the hypothalamic defence area (HVE). Following intravenous administration of diazepam (0.5 mg/kg), the pressor response and HVE induced by electrical stimulation of the hypothalamus were attenuated, as blood pressure (BP) dropped. Bilateral microinjection of flurazepam (200 micrograms in 0.5 microliters) or GABA (3 micrograms in 0.5 microliters) into the rostral ventrolateral medulla (rVLM) resulted in a significant decrease in BP, and pressor response during hypothalamic stimulation as well as reduction in the amount of HVE. Bilateral microinjection of picrotoxin (7.5 micrograms in 0.5 microliters) into the rVLM facilitated HVE and increased BP. Microinjection of flurazepam, GABA of the same doses into the caudal ventrolateral medulla (cVLM), however, had no such effect. The depressant effect of intravenous injection of diazepam could be prevented by bilateral microinjection of GABA receptor antagonist bicuculline (3 micrograms in 0.5 microliters) or picrotoxin (7.5 micrograms in 0.5 microliters) into the rVLM. Whereas bilateral microinjection of atropine (0.25 micrograms in 0.5 microliters), scopolamine (0.15 micrograms in 0.5 microliters), naloxone (0.5 micrograms in 0.5 microliters), strychnine (1 microgram in 0.5 microliters) into the rVLM no depressant effect was observed. These results suggest that the depressant effect of diazepam on BP, the pressor response and HVE may be mediated by activation of the GABA receptors in the rVLM.