Modulation of extracellular glutamate and pressor response to muscle contraction during NMDA-receptor blockade in the rostral ventrolateral medulla.
Recently our laboratory demonstrated increases in extracellular glutamate concentrations within the rostral ventrolateral medulla (RVLM) during static muscle contraction (Caringi, D.C., Maher, T., Chaiyakul, P., Asmundsson, G., Ishide, T., Ally, A. Pflügers Arch. Eur. J. Physiol., 435:465-471, 1998). In this study, we determined effects of microdialyzing D(-)2-amino-7-phosphonohepatanoic acid (AP-7), an NMDA-receptor antagonist, into the RVLM on changes in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during muscle contraction in anesthetized rats. Bilateral placements of microdialysis probes into the RVLM were verified by perfusing L-glutamate and obtaining a pressor response. Muscle contraction for 2 min, increased MAP and HR by 22+/-4 mmHg and 28+/-5 bpm, respectively. Extracellular glutamate as determined by microdialysis increased from 0.8+/-0.2 to 6.3+/-1.2 ng/5 microl. Microdialysis of AP-7 (1.0 microM) for 30 min inhibited contraction-evoked MAP and HR responses (10+/-3 mmHg and 13+/-3 bpm) and attenuated increases in glutamate during muscle contraction. Developed tensions did not differ during contractions before and after AP-7. Results demonstrate that NMDA-receptor blockade in the RVLM inhibits cardiovascular responses during static muscle contraction via a reduction in extracellular glutamate levels.
Reidman
D A
DA
Department of Physiology, University of New England, College of Osteopathic Medicine, Biddeford, ME 04005, USA.
Maher
T J
TJ
Chaiyakul
P
P
Ally
A
A
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid