Wendling W W, Chen D, Daniels F B, Monteforte M R, Fischer M B, Harakal C, Carlsson C
Department of Anesthesiology, Temple University Health Sciences Center, Philadelphia, Pennsylvania, USA.
Anesth Analg. 1996 Feb;82(2):264-8. doi: 10.1097/00000539-199602000-00009.
This pharmacologic study examines the direct cerebrovascular effects of N-methyl-D-aspartate (NMDA) receptor agonists and antagonists to determine whether large cerebral arteries have NMDA receptors. Bovine middle cerebral arteries were cut into rings to measure isometric tension development in vitro. Two competitive agonists, L-glutamate and NMDA, each had negligible effects on ring tension in the absence of exogenous vasoconstrictors. L-glutamate (in high concentrations) produced direct relaxation of potassium (K+)-constricted arteries, but the relaxation was not selective for L-glutamate, D-glutamate, or mannitol. Relaxation with L-glutamate was abolished when it was isosmotically substituted in the K(+)-rich medium. NMDA (in the absence or presence of glycine) and two competitive antagonists, 2-amino-5-phosphopentanoic acid (AP5) and (+/-)-3-(s-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), each had little effect on the tone of arteries preconstricted with potassium or the stable thromboxane A2 analog U-46,619. Three noncompetitive antagonists (S(+)-ketamine, dizocilpine, and dextrorphan) and their steroeisomers (R(-)-ketamine, (-)MK-801, and levorphanol) each produced dose-dependent relaxation of K(+)- or U-46,619-constricted arteries; relaxation was not selective for the (+) or (-) stereoisomers. These results suggest that large cerebral arteries lack NMDA receptors mediating constriction or relaxation. All noncompetitive antagonists dilated cerebral arteries, but by mechanisms that were not stereospecific.
本药理学研究检测了N-甲基-D-天冬氨酸（NMDA）受体激动剂和拮抗剂对脑血管的直接作用，以确定大脑大动脉是否存在NMDA受体。将牛大脑中动脉切成环状，以测量体外等长张力的变化。两种竞争性激动剂L-谷氨酸和NMDA，在没有外源性血管收缩剂的情况下，对环张力的影响均可忽略不计。L-谷氨酸（高浓度时）可使钾（K+）收缩的动脉直接舒张，但这种舒张对L-谷氨酸、D-谷氨酸或甘露醇并无选择性。当在富含K+的培养基中等渗替代L-谷氨酸时，其舒张作用消失。NMDA（无论有无甘氨酸存在）以及两种竞争性拮抗剂2-氨基-5-磷酸戊酸（AP5）和（±）-3-（s-羧基哌嗪-4-基）-丙基-1-膦酸（CPP），对预先用钾或稳定的血栓素A2类似物U-46,619收缩的动脉张力几乎没有影响。三种非竞争性拮抗剂（S(+)-氯胺酮、地佐环平、右啡烷）及其立体异构体（R(-)-氯胺酮、(-)MK-801、左啡烷）均可使K+或U-46,619收缩的动脉产生剂量依赖性舒张；这种舒张对（+）或（-）立体异构体并无选择性。这些结果表明，大脑大动脉缺乏介导收缩或舒张的NMDA受体。所有非竞争性拮抗剂均可使脑动脉扩张，但其机制并非立体特异性。
