Gören M Z, Onat F, Berkman K
Marmara University, School of Medicine, Department of Pharmacology and Clinical Pharmacology, Haydarpaşa, Istanbul, Turkey.
Eur J Pharmacol. 2000 Jan 24;388(1):77-84. doi: 10.1016/s0014-2999(99)00838-9.
The nuclei of the hypothalamus have been shown to be involved in central cardiovascular homeostasis. Recent studies suggest that glutamate-containing neurons have an important role in the regulation of central cardiovascular function. We report first on the effects of intracerebrally injected NMDA and non-NMDA receptor ligands on blood pressure and heart rate in conscious Sprague-Dawley rats. In the second part, we describe the effect of blockade of NMDA or kainate receptors in the paraventricular nucleus on glutamate receptor agonist-induced blood pressure responses. Intracerebroventricular injections of L-glutamic acid, NMDA and kainic acid produced increases in mean arterial pressure. Kainic acid produced significant decreases in heart rate. Microinjection of DL-2-amino-5-phosphonopentanoic acid (APV; 25 and 50 nmol), a competitive NMDA receptor antagonist, into the paraventricular nucleus blunted the increases in the mean arterial pressure evoked by intracerebroventricular injections of NMDA (1 nmol), whereas microinjection of dinitroquinoxaline (DNQX; 20, 40 and 80 pmol), which acts as an antagonist at kainate receptors, failed to antagonize the cardiovascular effects of intracerebroventricular kainic acid (10 pmol). Microinjections of NMDA (100 pmol) into the paraventricular nucleus produced pressor responses, but kainic acid (5 and 10 pmol) failed to affect either mean arterial pressure or heart rate. These results suggest participation of the glutamergic system in cardiovascular regulation via NMDA receptors located within the paraventricular nucleus of the hypothalamus in rats.
下丘脑的核团已被证明参与中枢心血管稳态调节。最近的研究表明，含谷氨酸的神经元在中枢心血管功能调节中起重要作用。我们首次报告了脑室内注射N-甲基-D-天冬氨酸（NMDA）和非NMDA受体配体对清醒Sprague-Dawley大鼠血压和心率的影响。在第二部分中，我们描述了室旁核中NMDA或海人酸受体阻断对谷氨酸受体激动剂诱导的血压反应的影响。脑室内注射L-谷氨酸、NMDA和海人酸可使平均动脉压升高。海人酸可使心率显著降低。向室旁核微量注射竞争性NMDA受体拮抗剂DL-2-氨基-5-磷酸戊酸（APV；25和50 nmol）可减弱脑室内注射NMDA（1 nmol）引起的平均动脉压升高，而作为海人酸受体拮抗剂的二硝基喹喔啉（DNQX；20、40和80 pmol）微量注射未能拮抗脑室内注射海人酸（10 pmol）的心血管效应。向室旁核微量注射NMDA（100 pmol）可产生升压反应，但海人酸（5和10 pmol）对平均动脉压或心率均无影响。这些结果表明，谷氨酸能系统通过大鼠下丘脑室旁核内的NMDA受体参与心血管调节。
