Barron K W, Pavelka S M, Garrett K M
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Brain Res. 1997 Oct 31;773(1-2):53-60. doi: 10.1016/s0006-8993(97)00882-2.
The present study employed neuropharmacological and receptor binding protocols to determine if diazepam-sensitive (DS) gamma-aminobutyric acid-A (GABA(A)) receptors in the nucleus tractus solitarius (NTS) participate in autonomic regulation of cardiovascular function. The first set of protocols was designed to determine if GABA(A) receptors in the NTS were functionally modulated by the benzodiazepine agonist, diazepam. Mean arterial pressure and heart rate responses to microinjection of GABAergic substances into the NTS were examined in urethane-anesthetized rats. Microinjection of the GABA(A) agonist isoguvacine into the NTS increased mean arterial pressure and heart rate, and these effects were blocked by the GABA(A) receptor antagonist, bicuculline. Preadministration of diazepam into the NTS potentiated the pressor actions of isoguvacine and had variable effects on heart rate changes. Flumazenil, a benzodiazepine antagonist, blocked the diazepam-induced potentiation of the pressor response to isoguvacine. The second protocol employed receptor autoradiography to examine the presence of DS and diazepam-insensitive (DI) GABA(A) receptors in the NTS. Autoradiography confirmed that DS GABA(A) receptors were present in the NTS; however, no measurable levels of DI GABA(A) receptors were detected. We conclude that GABA(A)-mediated integration of central autonomic control in the NTS is mediated solely by DS GABA(A) receptors.
本研究采用神经药理学和受体结合实验方法,以确定孤束核(NTS)中对安定敏感(DS)的γ-氨基丁酸A(GABA(A))受体是否参与心血管功能的自主调节。第一组实验旨在确定NTS中的GABA(A)受体是否受到苯二氮䓬类激动剂安定的功能调节。在乌拉坦麻醉的大鼠中,检测了向NTS微量注射GABA能物质后平均动脉压和心率的反应。向NTS微量注射GABA(A)激动剂异谷氨酰胺可升高平均动脉压和心率,且这些效应被GABA(A)受体拮抗剂荷包牡丹碱阻断。预先向NTS注射安定可增强异谷氨酰胺的升压作用,并对心率变化有不同影响。苯二氮䓬类拮抗剂氟马西尼可阻断安定诱导的对异谷氨酰胺升压反应的增强作用。第二组实验采用受体放射自显影术检测NTS中DS和对安定不敏感(DI)的GABA(A)受体的存在情况。放射自显影证实NTS中存在DS GABA(A)受体;然而,未检测到可测量水平的DI GABA(A)受体。我们得出结论,NTS中GABA(A)介导的中枢自主控制整合仅由DS GABA(A)受体介导。