Okada M, Buñag R D
Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City 66103, USA.
J Cardiovasc Pharmacol. 1995 Sep;26(3):363-71. doi: 10.1097/00005344-199509000-00004.
To examine how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) affects baroreflex regulation, reflex heart rate and renal nerve responses were recorded in anesthetized rats after bilateral injections of muscimol or bicuculline into the nucleus tractus solitarius (NTS). Blood pressure, heart rate, and renal nerve activity were increased by the GABA agonist muscimol and decreased by the GABA antagonist bicuculline. Control injections of the vehicle alone were ineffective. More importantly, all reflex responses later induced by infusing phenylephrine or sodium nitroprusside intravenously were reduced by muscimol. The magnitude of the reflex bradycardia and sympathoinhibition caused by phenylephrine, as well as that of the reflex tachycardia and sympathoexcitation caused by sodium nitroprusside, diminished after NTS injections of muscimol. By contrast, the same reflex responses tended to be enhanced after NTS injections of bicuculline, but most changes were not significant. If GABA acts on receptors located on second-order neurons in the NTS, then muscimol would inhibit those neurons, whereas bicuculline would prevent endogenous GABA from reaching them. Thus muscimol would reduce reflex responsiveness by inhibiting all second-order neurons, whereas bicuculline would enhance it by protecting the same neurons from inhibition by endogenous GABA.
为研究抑制性神经递质γ-氨基丁酸(GABA)如何影响压力感受性反射调节,在孤束核(NTS)双侧注射蝇蕈醇或荷包牡丹碱后,记录麻醉大鼠的反射性心率和肾神经反应。GABA激动剂蝇蕈醇可使血压、心率和肾神经活动增加,而GABA拮抗剂荷包牡丹碱则使其降低。单独注射溶剂的对照注射无效。更重要的是,静脉输注去氧肾上腺素或硝普钠后随后诱导的所有反射反应均被蝇蕈醇减弱。在NTS注射蝇蕈醇后,去氧肾上腺素引起的反射性心动过缓和交感抑制的幅度,以及硝普钠引起的反射性心动过速和交感兴奋的幅度均减小。相比之下,在NTS注射荷包牡丹碱后,相同的反射反应往往增强,但大多数变化不显著。如果GABA作用于NTS中二级神经元上的受体,那么蝇蕈醇会抑制这些神经元,而荷包牡丹碱会阻止内源性GABA作用于它们。因此,蝇蕈醇会通过抑制所有二级神经元来降低反射反应性,而荷包牡丹碱会通过保护相同神经元免受内源性GABA的抑制来增强反射反应性。