Tonic sympathetic chemoreflex after blockade of respiratory rhythmogenesis in the rat

1. We sought to determine whether the increase in sympathetic nerve discharge (SND) caused by carotid chemoreceptor stimulation requires the integrity of ventrolateral medullary structures involved in generating respiratory rhythm and pattern. Experiments were done in urethane-anaesthetized, vagotomized, aortic deafferented, ventilated rats except when indicated (see paragraph 3). 2. Brief hypoxia (N2 for 5-12 s) or I.V. NaCN (50-100 micrograms kg-1) activated SND in bursts synchronized with the phrenic nerve discharge (PND). No effect was produced in chemo-deafferented rats. 3. In unanaesthetized vagotomized decerebrated rats, ligation of the internal carotid arteries preserved peripheral chemoreceptor function but abolished baroreflexes. In this preparation, stimulation of peripheral chemoreceptors (N2 for 2-6 s) also activated SND in bursts synchronized with PND. 4. Bilateral microinjection of the GABAA receptor agonist muscimol into the caudal ventrolateral medulla (CVLM) instantly blocked the sympathetic baroreflex, eliminated PND at rest and during chemoreceptor stimulation but did not change the mean increase in SND produced by chemoreceptor stimulation. Sympathoactivation in response to chemoreceptor stimulation became tonic after 1-13 min and was still totally dependent on the integrity of the carotid sinus nerves. 5. Muscimol injection instantly eliminated the respiratory outflow of the Xth and XIIth cranial nerves, both at rest and during chemoreceptor stimulation. 6. Muscimol eliminated the on-off respiratory pattern of neurons in the rostral ventrolateral medulla (RVLM). During chemoreceptor stimulation, these cells became activated or inhibited tonically. 7. Muscimol injection raised the resting discharge rate of vasomotor presympathetic cells in RVLM, blocked their baroreceptor inputs but did not change the magnitude of their excitation by chemoreceptor stimulation. Muscimol injection eliminated their respiratory modulation. 8. In conclusion, the sympathetic response to chemoreceptor stimulation may be due to convergence and integration in RVLM of two processes: respiration-independent excitatory input to RVLM neurons and respiratory patterning of their activities via inputs from the pre-Bötzinger complex.