Florentino A, Varga K, Kunos G
Laboratory of Physiological and Pharmacological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Brain Res. 1990 Dec 10;535(2):264-70. doi: 10.1016/0006-8993(90)91609-k.
The effects of baclofen microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and baroreflex bradycardia were studied in urethane-anesthetized rats. Baclofen caused dose-dependent pressor and tachycardic effects and inhibited the reflex bradycardia elicited by i.v. phenylephrine. The effects of baclofen were inhibited by similarly administered GABAB receptor antagonists, phaclofen and 2-OH-saclofen, or the non-NMDA glutamate receptor antagonist, DNQX, or by pretreatment of rats with intracisternally administered pertussis toxin. DNQX and pertussis toxin, but not the NMDA antagonist, MK-801, also inhibited baroreflex bradycardia. Intra-NTS injections of glutamate caused hypotension and bradycardia, which were potentiated by baclofen, and were not affected by either DNQX or MK-801 or by pretreatment with pertussis toxin. These findings indicate that the cardiovascular effects of stimulation of GABAB receptors in the NTS are due, at least in part, to inhibition of the depressor baroreflex response. Inhibition of the release and/or postsynaptic action of an excitatory amino acid transmitter other than glutamate is the most likely mechanism.
在乌拉坦麻醉的大鼠中，研究了向孤束核（NTS）微量注射巴氯芬对血压、心率和压力感受性反射性心动过缓的影响。巴氯芬引起剂量依赖性的升压和心动过速作用，并抑制静脉注射去氧肾上腺素诱发的反射性心动过缓。巴氯芬的作用被同样给药的GABAB受体拮抗剂、法氯芬和2-羟基-氯苯氨丁酸，或非NMDA谷氨酸受体拮抗剂、DNQX，或通过向大鼠脑池内注射百日咳毒素预处理所抑制。DNQX和百日咳毒素，但不是NMDA拮抗剂MK-801，也抑制压力感受性反射性心动过缓。向NTS内注射谷氨酸引起低血压和心动过缓，巴氯芬可增强其作用，且不受DNQX或MK-801影响，也不受百日咳毒素预处理的影响。这些发现表明，刺激NTS中的GABAB受体对心血管的影响至少部分是由于抑制降压压力感受性反射反应。抑制谷氨酸以外的兴奋性氨基酸递质的释放和/或突触后作用是最可能的机制。
