D'Amico M, Warner T D
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London.
Br J Pharmacol. 1995 Dec;116(7):2787-9. doi: 10.1111/j.1476-5381.1995.tb15927.x.
Microinjection of N-methyl-D-aspartate (NMDA) (0.068 to 6.8 nmol) into the periaqueductal gray area (PAG) of anaesthetized rats caused dose-dependent increases in blood pressure. Preinjection (10 min before) of FR 139317 (an ETA receptor selective antagonist; 5 nmol) or SB 209670 (an ETA/ETB receptor non-selective antagonist; 5 nmol) to the PAG reduced the pressor response to NMDA whereas BQ-788 (an ETB receptor selective antagonist; 5 nmol) did not affect the NMDA-induced hypertension. Pretreatment with DL-2-amino-5-phosphono valeric acid (2-APV) (an NMDA receptor selective antagonist, 5 nmol) also abolished the pressor response induced by NMDA. Dose-dependent increases in blood pressure induced by injection of angiotensin II (0.1-10 nmol) to the PAG were unaffected by FR 139317 or SB 209670. Thus, our data indicate that endogenous ET-1, via an action on ETA receptors, contributes to the pressor effects of NMDA within the brain.
向麻醉大鼠的中脑导水管周围灰质区域（PAG）微量注射N-甲基-D-天冬氨酸（NMDA）（0.068至6.8纳摩尔）可导致血压呈剂量依赖性升高。在向PAG注射FR 139317（一种ETA受体选择性拮抗剂；5纳摩尔）或SB 209670（一种ETA/ETB受体非选择性拮抗剂；5纳摩尔）之前（提前10分钟）进行预注射，可降低对NMDA的升压反应，而BQ-788（一种ETB受体选择性拮抗剂；5纳摩尔）不影响NMDA诱导的高血压。用DL-2-氨基-5-磷酸戊酸（2-APV）（一种NMDA受体选择性拮抗剂，5纳摩尔）进行预处理也可消除NMDA诱导的升压反应。向PAG注射血管紧张素II（0.1 - 10纳摩尔）所诱导的血压剂量依赖性升高不受FR 139317或SB 209670的影响。因此，我们的数据表明，内源性ET-1通过作用于ETA受体，在脑内对NMDA的升压作用有贡献。
