Glutamate neurotransmission and nitric oxide interaction within the ventrolateral medulla during cardiovascular responses to muscle contraction.

Abstract We previously reported that nitric oxide, within the RVLM and CVLM, plays an opposing role in modulating cardiovascular responses during static muscle contraction [B.J. Freda, R.S. Gaitonde, R. Lillaney, A. Ally, Cardiovascular responses to muscle contraction following microdialysis of nitric oxide precursor into ventrolateral medulla, Brain Res. 828 (1999) 60–67]. In this study, we determined whether the effects of administering l -arginine, a precursor for the synthesis of nitric oxide, and N G -monomethyl- l -arginine ( l -NMMA), a nitric oxide synthase inhibitor, into the rostral (RVLM) and caudal (CVLM) ventrolateral medulla on cardiovascular responses elicited during static muscle contraction were mediated via an alteration of localized glutamate concentrations using microdialysis techniques. In experiments within the RVLM ( n =8), muscle contraction increased MAP and HR by 21±2 mm Hg and 22±3 bpm, respectively. Glutamate increased from 1.1±0.4 to 4.4± 0.6 ng/5 μl measured from bilateral RVLM areas. Microdialysis of l -arginine (1.0 μM) for 30 min attenuated the contraction-evoked increases in MAP, HR, and glutamate levels. After subsequent microdialysis of l -NMMA (1.0 μM) into the RVLM, contraction augmented the pressor and tachycardic responses and glutamate release. In experiments within CVLM ( n =8), muscle contraction increased MAP and HR by 22±3 mm Hg and 20±2 bpm, respectively. Glutamate increased from 0.8±0.4 to 3.6±0.6 ng/5 μl measured from the CVLM. l -Arginine augmented the cardiovascular responses and glutamate release and l -NMMA attenuated all the effects. Results suggest that nitric oxide within the RVLM and CVLM plays opposing roles in modulating cardiovascular responses during static exercise via decreasing and increasing, respectively, extracellular glutamate levels.