Neuronal Nitric Oxide Synthase (nNOS) blockade within the ventrolateral medulla differentially modulates cardiovascular responses and nNOS expression during static skeletal muscle contraction

Nitric oxide (NO) is synthesized from L-arginine through the activity of the enzyme, NO synthase (NOS). Previous studies have demonstrated the role of the 3 isoforms of NOS, namely endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) in cardiovascular regulation. Local blockade of nNOS in RVLM vs. CVLM differentially alters local glutamate and GABA release, and thereby results in opposite cardiovascular responses to static muscle contraction (Brain Res. 2003, 977, 80-89). In this study, we examined whether nNOS antagonism within the RVLM and CVLM affected cardiovascular responses during the exercise pressor reflex and simultaneously modulated medullary nNOS protein expression using anesthetized rats. Bilateral microdialysis of a selective nNOS antagonist, 1-(2-trifluoromethylphenyl)-imidazole (TRIM, 1.0 μM) for 120 min into the RVLM, potentiated cardiovascular responses during a static muscle contraction. Western blot analysis of nNOS expression within the RVLM showed significant attenuation of the protein when compared to the data obtained from control animals microdialyzed with vehicle. In contrast, bilateral application of TRIM into the CVLM attenuated cardiovascular responses during muscle contractions and increased nNOS protein expression within the CVLM. These results demonstrated that nNOS protein expression within the brainstem was pharmacologically altered by nNOS blockade within the RVLM or CVLM, which in turn might have contributed to the augmentation or attenuation of cardiovascular responses, respectively, during static exercise.