Effect of intrathecal amino acid receptor antagonists on basal blood pressure and pressor responses to brainstem stimulation in normotensive and hypertensive rats

E. Mills, J. Minson, G. Drolet, J. Chalmers

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    43 Citations (Scopus)

    Abstract

    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 Cl area or the serotonincontaining 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 Cl 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. It is possible that the increased activity of bulbospinal excitatory amino acid pathways from Cl and B3 areas of RVLM contributes to the hypertension observed in SHR and SPR.

    Original languageEnglish
    Pages (from-to)877-883
    Number of pages7
    JournalJournal of Cardiovascular Pharmacology
    Volume15
    Issue number6
    DOIs
    Publication statusPublished - Jun 1990

    Keywords

    • Amino acid antagonists
    • Amino acids
    • Blood pressure
    • Rat
    • Rostral ventrolateral medulla
    • Spinal cord

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