Mills E, Minson J, Drolet G, Chalmers J
Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia.
J Cardiovasc Pharmacol. 1990 Jun;15(6):877-83. doi: 10.1097/00005344-199006000-00004.
The importance of spinal cord amino acid receptors in the regulation of blood pressure was investigated in normotensive (Wistar Kyoto, WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive (SPR) rats. Also investigated was the possible role of these spinal cord receptors in mediating pressor changes evoked by electrical stimulation of two separate areas of the rostral ventrolateral medulla (RVLM) containing different neuronal populations, either the adrenaline-containing C1 area or the serotonin-containing B3 area. Intrathecal administration of the amino acid receptor antagonist kynurenate (KYN), or the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2APV), reduced basal blood pressure in anesthetized SHR and SPR in a dose-dependent manner, but were ineffective or elicited only small decreases in WKY. In all three strains, electrical stimulation in RVLM, in either the C1 or B3 area, evoked frequency-dependent pressor responses. Administration of 2APV or KYN was effective in attenuating these pressor responses in all three strains of rats. The effects of stimulation in the RVLM-B3 area were virtually abolished by administration of 2APV followed by the serotonin receptor antagonist methysergide. The results suggest that spinal cord excitatory amino acid receptors are important in blood pressure regulation in rats. Amino acid receptors, perhaps of the NMDA subtype, appeared to mediate pressor responses to stimulation of the RVLM-C1 and RVLM-B3 regions in both normotensive and hypertensive animals. On the other hand, excitatory amino acid receptor antagonists reduced basal blood pressure only in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在正常血压的(Wistar Kyoto,WKY)、自发性高血压的(SHR)和易中风自发性高血压的(SPR)大鼠中,研究了脊髓氨基酸受体在血压调节中的重要性。还研究了这些脊髓受体在介导由电刺激延髓头端腹外侧区(RVLM)两个不同区域诱发的升压变化中可能起的作用,这两个区域包含不同的神经元群体,即含肾上腺素的C1区或含5-羟色胺的B3区。鞘内注射氨基酸受体拮抗剂犬尿烯酸(KYN)或选择性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂2-氨基-5-磷酸戊酸(2APV),以剂量依赖的方式降低了麻醉的SHR和SPR的基础血压,但对WKY无效或仅引起小幅下降。在所有三个品系中,RVLM中C1区或B3区的电刺激均诱发频率依赖性升压反应。在所有三个品系的大鼠中,注射2APV或KYN均可有效减弱这些升压反应。在注射2APV后再注射5-羟色胺受体拮抗剂麦角新碱,几乎消除了RVLM-B3区刺激的效应。结果表明,脊髓兴奋性氨基酸受体在大鼠血压调节中很重要。氨基酸受体,可能是NMDA亚型,似乎介导了正常血压和高血压动物对RVLM-C1区和RVLM-B3区刺激的升压反应。另一方面,兴奋性氨基酸受体拮抗剂仅降低了高血压大鼠的基础血压。(摘要截断于250字)