PVN GABA(A) receptor antagonism profoundly alters the frequency components in sympathetic nerves in a rat model, highlighting central mechanisms of sympathetic regulation.
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Supports central GABAergic control of sympathetic patterning in rats; leaves open translation to human disease.
Autospectral and coherence analyses were used to determine the effect of paraventricular nucleus (PVN) GABA(A) receptor antagonism [microinfusion or microinjections of bicuculline methiodide (BMI) 100 pmoles] on sympathetic nerve discharge (SND) frequency components (bursting pattern and relationships between discharges in regionally selective nerves) in alpha-chloralose-anesthetized rats. SND was recorded from the renal, splenic, and lumbar nerves. The following observations were made. First, PVN BMI microinjections, but not PVN saline or cortical BMI microinjections, transformed the cardiac-related SND bursting pattern in baroreceptor-innervated rats to one characterized by the presence of low-frequency bursts not synchronized to the cardiac cycle or phrenic nerve discharge bursts. Second, SND pattern changes were similar in the renal, splenic, and lumbar nerves, and peak coherence values relating low-frequency bursts in sympathetic nerve pairs (renal-splenic, renal-lumbar, and splenic-lumbar) were significantly increased from preinjection control after PVN BMI microinjection. Third, PVN BMI microinjections significantly increased the coupling between low-frequency SND bursts in baroreceptor-denervated rats. Finally, PVN BMI-induced changes in the SND bursting pattern were not observed after PVN pretreatment with muscimol (GABA agonist, 1 nmole). We conclude that PVN GABA(A) receptor antagonism profoundly alters the frequency components in sympathetic nerves.
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Kenney et al. (2001) studied this question.
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