Hasséssian H, Prat A, De Champlain J, Couture R
Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.
Eur J Pharmacol. 1991 Sep 4;202(1):51-60. doi: 10.1016/0014-2999(91)90252-l.
The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.
在清醒大鼠中研究了P物质（SP）和γ-氨基丁酸（GABA）对心血管交感神经节前神经元的脊髓调节作用。在T-9脊髓水平鞘内注射GABAA受体拮抗剂荷包牡丹碱，可引起平均动脉压（MAP）和心率（HR）升高，分别在5.0和0.5 nmol时达到最大值。GABAB受体拮抗剂巴氯芬在高达2 μmol时未引起心血管变化，而10 μmol时可引起MAP和HR升高。GABAA受体激动剂蝇蕈醇可使MAP降低，在5.0 nmol时达到最大值，对HR无影响。GABAB受体激动剂巴氯芬在高达5.0 nmol时无心血管作用，而50和100 nmol时可引起MAP和HR下降。对SP（16.25 nmol，T-9）的升压反应以剂量相关的方式被0.5 - 50 nmol的蝇蕈醇或巴氯芬拮抗，在辣椒素处理的动物中，40 nmol GABA仍可抑制对SP的升压反应。然而，当在T-2注射SP时，50 nmol巴氯芬可阻断MAP和HR的升高。同样，50 nmol蝇蕈醇可阻断15 nmol促甲状腺激素释放激素诱导的MAP和HR升高。相比之下，50 nmol甘氨酸未能改变在T-9或T-2共同注射SP时的心血管反应。发现巴氯芬在T-9水平注射时可显著降低肾上腺素的基础释放。这些结果为通过GABAA和GABAB受体介导的对心血管交感神经节前神经元可能存在的强直性GABA能抑制性输入提供了药理学证据。
