Evidence for-y-Aminobutyric Acid Mediation of the Sympathetic Nerve Inhibitory Response to Vagal Afferent Stimulation

The involvement of y-aminobutync acid (GABA) in the vagal-stimulated reflex inhibition of sympathetic nerve discharge (SND) was investigated in the cat. Computer summation was used to assess the sympathoinhibitory response to vagal afferent stim-ulation and the resultant changes seen with agents known to effect GABAergic neurotransmission. The GABA antagonists picrotoxin and bicuculline at 0.25 to 1.0 mg/kg i.v. attenuated the vagal sympathetic inhibitory response, but increased the 1:1 locking of SND to the arterial pulse. Conversely, the GABA agonist diazepam at 0.3 mg/kg i.v. potentiated the vagal sym-pathoinhibition, reduced total SND and diminished SND locking to the arterial pulse. Picrotoxin also blocked the vagal sympa-thoinhibitory response in midcollicular transected cats and when applied topically to the dorsal brain stem. Midcollicular transec-tion forestalled the irregular SND spiking normally seen with picrotoxin in the intact cat, thus resulting in improved 3 cycle/ Sec SND penodicity. None of these drug-induced changes ef-fected the SND shutoff response to vasopressor tests, however. These results suggest that GABA plays a role in the SND inhibitory response to vagal afferent stimulation in the brain stem, independent of the sinoarterial baroreceptors, and may also be involved in the entrainment of SND to the arterial pulse. The anatomy, physiology and pathophysiologic reflexes me-diated by the vagal afferent nerve fibers have been investigated extensively in recent years. A large number of myelinated and unmyelinated afferent neurons are present in the vagal trunks, emanating from aortic, cardiopulmonary and gastroesophagea