[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.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005117:Cardiac Complexes, Premature / Q000503:physiopathology*; D003975:Diazepam / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects
D011963:Receptors, GABA-A; D003975:Diazepam