Effect of intrathecal amino acid receptor antagonists on basal blood pressure and pressor responses to brainstem stimulation in normotensive and hypertensive rats.
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)
Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia.
E
E
Mills
J
J
Minson
G
G
Drolet
J
J
Chalmers
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000596:Amino Acids; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001933:Brain Stem / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008784:Methysergide / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D008784:Methysergide