Effects of ventrolateral medullary NMDA-receptor antagonism on biogenic amines and pressor response to muscle contraction.
Effects of D(-)2-amino-7-phosphonohepatanoic acid (AP-7), an N-methyl-D-aspartic acid (NMDA) receptor antagonist, administered into rostral ventrolateral medulla (RVLM) on changes in mean arterial pressure (MAP), heart rate (HR), extracellular levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) during static muscle contraction were investigated in anesthetized rats. Tibial nerve stimulation-evoked muscle contraction increased MAP and HR by 25+/-3 mmHg and 29+/-4 bpm, respectively. Microdialysis of AP-7 (1 microM) into the RVLM for 30 min attenuated the contraction-evoked cardiovascular responses with similar developed muscle tensions, without baseline HR or blood pressure changes. Administration of AP-7 into the caudal ventrolateral medulla had no effect on MAP or HR responses during contraction. Muscle contraction increased extracellular 5-HT in the RVLM by 144+/-35%, DA by 104+/-15% and NE by 62+/-12%. Perfusion of AP-7 for 30 min into the RVLM attenuated contraction-evoked increases in monoamines, concomitant to attenuating cardiovascular responses. Results demonstrate that NMDA-receptor blockade within the RVLM, but not the CVLM, inhibits cardiovascular responses during muscle contraction. Furthermore, NMDA receptor antagonism within the RVLM results in a decrease of biogenic amine release during muscle contraction, suggesting that extracellular biogenic amine concentrations are modulated by NMDA receptors.
Asmundsson
G
G
Department of Pharmacology, University of New England, College of Osteopathic Medicine, Biddeford, ME 04005, USA.
Mokler
D J
DJ
Ally
A
A
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D017072:Neostriatum / Q000737:chemistry / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism
D001679:Biogenic Amines; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid; D004298:Dopamine; D009638:Norepinephrine