Role of nitric oxide in the ventrolateral medulla on cardiovascular responses and glutamate neurotransmission during mechanical and thermal stimuli.

We have previously reported that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor blockade within the rostral ventrolateral medulla (RVLM) attenuates cardiovascular responses and extracellular concentrations of glutamate during mechanical, but not during thermal stimulation [Pharmacol. Res. 43 (2001) 47]. In this study, we examined the role of nitric oxide (NO) within the RVLM on cardiovascular responses and glutamate release during both mechanical and thermal nociception using anesthetized Sprague-Dawley rats. Two types of stimuli were studied, both activating peripheral Adelta and C fiber polymodal nociceptors. Noxious mechanical stimuli were given by applying a bilateral hindpaw pinch for 5s. The noxious thermal stimuli were generated by immersing the metatarsus of both hindpaws in a water bath at a temperature of 52 degrees C for 5s. Mechanical stimulation of both hindlimb extremities increased mean arterial pressure (MAP), heart rate (HR), and extracellular fluid glutamate by 14+/-2 mmHg, 35+/-5 bpm, and 1.4+/-0.3 ng/5 microl, respectively (n=8). Similar responses were observed following thermal stimulation: 40+/-4 mmHg, 44+/-6 bpm, and 0.97+/-0.2 ng/5 microl (n=8). Bilateral microdialysis of L-arginine (1.0 microM), a nitric oxide precursor, into the RVLM had no effects on MAP, HR, and glutamate increases during mechanical stimulation. However, L-arginine attenuated these responses during thermal nociception. Subsequent administration of L-NMMA (1.0 microM), a NOS inhibitor, reversed the attenuations. These results show that nitric oxide most likely plays a role in modulating cardiovascular responses by altering glutamate concentrations within the RVLM during thermal but not mechanical nociception. Overall, the present study delineates the differential central integrative mechanisms that regulate processing of sensory impulses arising from peripheral stimulation.