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

We previously reported that nitric oxide, within the RVLM and CVLM, plays a n opposing role in modulating cardiovascular responses during static muscle contraction [B,J. Freda, R.S. Gaitonde, R, Lillaney, A. Ally, Cardiovascul ar 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 pr ecursor for the synthesis of nitric oxide, and N-G-monomethyl-L-arginine (L -NMMA), a nitric oxide synthase inhibitor, into the rostral (RVLM) and caud al (CVLM) ventrolateral medulla on cardiovascular responses elicited during static muscle contraction were mediated via an alteration of localized glu tamate concentrations using microdialysis techniques. In experiments within the RVLM (n=8), muscle contraction increased MAP and HR by 21+/-2 mm Hg an d 22+/-3 bpm, respectively. Glutamate increased from 1.1+/-0.4 to 4.4+/-0.6 ng/5 mu l measured from bilateral RVLM areas. Microdialysis of L-arginine (1.0 mu M) for 30 min attenuated the contraction-evoked increases in MAP, H R, and glutamate levels. After subsequent microdialysis of L-NMMA (1.0 mu M ) into the RVLM, contraction augmented the presser and tachycardic response s and glutamate release. In experiments within CVLM (n=8), muscle contracti on increased MAP and HR by 22+/-3 mm Hg and 20+/-2 bpm. respectively. Gluta mate increased from 0.8+/-0.4 to 3.6+/-0.6 ng/5 mu l measured from the CVLM . L-Arginine augmented the cardiovascular responses and glutamate release a nd L-NMMA attenuated all the effects. Results suggest that nitric oxide wit hin the RVLM and CVLM plays opposing roles in modulating cardiovascular res ponses during static exercise via decreasing and increasing, respectively, extracellular glutamate levels. (C) 2000 Elsevier Science B.V. All rights r eserved.