GABA In Paraventricular Nucleus Regulates Adipose Afferent Reflex In Rats

BackgroundWhite adipose tissues (WAT) are innervated by both sensory fibers and efferent sympathetic fibers. The efferent and afferent neural innervation of WAT are involved in body fat regulation. Chemical stimulation of white adipose tissues (WAT) induces sympathetic activation. The sympatho-excitatory reflex, adipose afferent reflex (AAR) may be important in promoting lipolysis and energy expenditure. Hypothalamic paraventricular nucleus (PVN) is an important integrative site within the brain in control of sympathetic outflow and cardiovascular activity, and also plays an important role in the control of AAR. The activation of ionotropic glutamate receptors in the PVN is involved in the AAR-induced production of superoxide anions, and NAD(P)H oxidase-derived superoxide anions in the PVN contributes to the tonic modulation of AAR. Furthermore, activation of melanocortin-4 receptors in the PVN enhances the AAR via a cAMP-PKA pathway. It is known that y-aminobutyric acid (GABA) in the PVN reduces blood pressure and sympathetic outflow. Ionotropic GABAA receptors and metabotropic GABAB receptors are involved in regulating blood pressure and sympathetic outflow in normal and hypertensive rats. The present study is designed to determine whether GABA in the PVN plays an inhibitory role in modulating AAR.Objective1.To determine whether GABA receptor in PVN regulates AAR.2.To determine whether GABA-transaminase in PVN regulates AAR.MethodsExperiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT) afferent nerve. Bilateral PVN microinjection of the GAB AA receptor agonist isoguvacine, the GAB AB receptor agonist baclofen, the GABAA receptor antagonist gabazine, the GABAB receptor antagonist CGP-35348, or the selective GABA-transaminase inhibitor vigabatrin, respectively.Results1. Isoguvacine or baclofen dose-dependently decreased baseline RSNA and MAP. Either isoguvacine or baclofen dose-dependently inhibited the AAR.2. Gabazine or CGP35348 increased baseline RSNA and MAP.Gabazine enhanced the AAR, and pretreatment with gabazine abolished isoguvacine-induced AAR inhibition. CGP35348 had no significant effect on AAR, but pretreatment with CGP35348 abolished baclofen-induced AAR inhibition.3. Vigabatrin reduced baseline RSNA and MAP, and completely inhibited the AAR. The effect of vigabatrin was attenuated by gabazine or CGP35348, and abolished by combined gabazine and CGP35348.ConclusionsActivation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockage of GABAA receptors in the PVN enhances the AAR. Endogenous GAB A in the PVN plays an important role in regulating the AAR.