Hong Y, Henry J L
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Eur J Pharmacol. 1991 Aug 29;201(2-3):171-7. doi: 10.1016/0014-2999(91)90341-m.
Our earlier observation that intrathecal administration of L- and D-baclofen had different effects on sympathetic output regulating arterial pressure and heart rate in the rat prompted the present study which was designed to determine whether intrathecal administration of GABA elicits a phaclofen-reversible effect on arterial pressure and/or heart rate and whether this effect mimics that of L-baclofen or that of D-baclofen. Following intrathecal administration of the GABAA antagonist, bicuculline (10 nmol), at the T9 level, administration of GABA at a dose of 5 mumol (n = 8) decreased arterial pressure and heart rate by about 25 mm Hg and 45 bpm, respectively. The responses started at 1-2 min and lasted 3-20 min; comparison was made with rats given NaCl (5 mumol; n = 5), which was without effect on arterial pressure and heart rate. In rats pretreated with both bicuculline and the GABAB antagonist, phaclofen (5 mumol intrathecally; n = 9), the effect of GABA on arterial pressure was attenuated and the effect of GABA on heart rate was absent; comparisons were made with rats given bicuculline, phaclofen and NaCl (n = 5) and with rats given bicuculline, NaCl and GABA (n = 6). These data suggest that there is a phaclofen-reversible effect of GABA in spinal pathways regulating sympathetic output and that this effect of GABA resembles that L-baclofen reported in our earlier study.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前观察到,鞘内注射L-和D-巴氯芬对大鼠调节动脉血压和心率的交感神经输出有不同影响,这促使我们开展了本研究,旨在确定鞘内注射GABA是否会对动脉血压和/或心率产生一种能被巴氯芬逆转的效应,以及这种效应是类似于L-巴氯芬还是D-巴氯芬的效应。在T9水平鞘内注射GABAA拮抗剂荷包牡丹碱(10 nmol)后,以5 μmol的剂量注射GABA(n = 8)可使动脉血压和心率分别降低约25 mmHg和45次/分钟。反应在1 - 2分钟开始,持续3 - 20分钟;与注射氯化钠(5 μmol;n = 5)的大鼠进行比较,氯化钠对动脉血压和心率无影响。在用荷包牡丹碱和GABAB拮抗剂巴氯芬预处理的大鼠中(鞘内注射5 μmol;n = 9),GABA对动脉血压的效应减弱,对心率的效应消失;与注射荷包牡丹碱、巴氯芬和氯化钠的大鼠(n = 5)以及注射荷包牡丹碱、氯化钠和GABA的大鼠(n = 6)进行比较。这些数据表明,在调节交感神经输出的脊髓通路中,GABA存在一种能被巴氯芬逆转的效应,且GABA的这种效应类似于我们早期研究中报道的L-巴氯芬的效应。(摘要截短至250字)