Effects of nitric oxide and GABA interaction within ventrolateral medulla on cardiovascular responses during static muscle contraction

We hypothesized that nitric oxide (NO) has opposing roles in regulating cardiovascular responses within the rostral (RVLM) and caudal (CVLM) ventrolateral medulla by modulating release of γ-aminobutyric acid (GABA). We have measured GABA concentrations within the RVLM and CVLM during increases in mean arterial pressure (MAP) and heart rate (HR) following a 2-min tibial nerve stimulation-evoked static muscle contraction before and after microdialysis of the NO precursor, L-arginine (1.0 μM), for 30 min, and after the NO inhibitor, L-NMMA (1.0 μM), for 30 min. In eight anesthetized rats, muscle contraction significantly increased MAP, HR and GABA levels within the RVLM area (from 0.53±0.09 to 1.22±0.10 ng/10 μl). Following microdiaysis of L-arginine, muscle contraction augmented GABA levels (from 0.45±0.07 to 2.18±0.09 ng/10 μl) and attenuated changes in MAP and HR. Subsequent application of L-NMMA significantly decreased GABA levels (from 0.47±0.08 to 0.22±0.07 ng/10 μl) but potentiated MAP and HR responses to a muscle contraction. In contrast, muscle contraction significantly increased MAP and HR but decreased GABA concentrations within the CVLM (from 1.20±0.20 to 0.78±0.17 ng/10 μl). Following microdiaysis of L-arginine, muscle contraction significantly attenuated GABA levels (from 1.34±0.19 to 0.33±0.10 ng/10 μl) and augmented changes in MAP and HR in response to muscle contraction. A subsequent microdialysis of L-NMMA into the CVLM reversed the effects of L-arginine. These results demonstrate that NO within the RVLM and CVLM differentially modulates cardiovascular responses during static muscle contraction and that NO influences exercise-induced cardiovascular responses by modulating GABA release within the ventrolateral medulla.