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 i nvestigated in anesthetized rats. Tibial nerve stimulation-evoked musc le contraction increased MAP and HR by 25 +/- 3 mmHg and 29 +/- 4 bpm, respectively. Microdialysis of AP-7 (1 mu M) into the RVLM for 30 min attenuated the contraction-evoked cardiovascular responses with simil ar developed muscle tensions, without baseline HR or blood pressure ch anges. Administration of AP-7 into the caudal ventrolateral medulla ha d no effect on MAP or HR responses during contraction. Muscle contract ion 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 R VLM attenuated contraction-evoked increases in monoamines, concomitant to attenuating cardiovascular responses. Results demonstrate that NMD A-receptor blockade within the RVLM, but not the CVLM, inhibits cardio vascular responses during muscle contraction. Furthermore, NMDA recept or antagonism within the RVLM results in a decrease of biogenic amine release during muscle contraction, suggesting that extracellular bioge nic amine concentrations are modulated by NMDA receptors. (C) 1998 Els evier Science Ireland Ltd. All rights reserved.