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.