Plasticity of GABAergic Mechanisms Within the Nucleus of the Solitary Tract in Hypertension

摘要

Adaptive changes have long been recognized to occur in the heart and vasculature in response to chronic hypertension. What might be less well-appreciated is the fact that chronically increased blood pressure is also associated with adaptive changes in neurons within the central nervous system (CNS). Changes in the properties of ligand-gated and voltage-gated channels have been described in a variety of neurons in a variety of central nuclei and in a variety of models of hypertension.Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in virtually every region in the adult brain. Microinjections of GABA and GABA receptor subtype-selective agonists and antagonists have been performed within various cardiovascular-related regions of the CNS. In every cardiovascular-related region of the CNS tested, activation of GABA receptors alters cardiovascular function. This is likely attributable to the ubiquitous role of GABA within the CNS. GABAergic inhibition can be mediated by activation of receptors located in presynaptic and postsynaptic loci. Two major subtypes of the GABA receptor exist: the GABAA receptor is a pentameric, chloride ionophore that primarily mediates postsynaptic inhibition,1 whereas the GABAB receptor is a G-protein-coupled receptor that can induce reductions in calcium conductance to mediate presynaptic inhibition and increases in potassium conductance to mediate postsynaptic inhibition.2GABAergic inhibition of central neurons can result in pressor or depressor responses depending on the central site being examined. Pressor responses are often assumed to be the result of GABAergic inhibition of neurons that reduce sympathetic discharge. Depending on the specific area being studied, GABA injections into the CNS can also alter vagal cardiac function and levels of vasoactive hormones such as vasopressin and angiotensin, in addition to changes in sympathetic outflow.3,4In addition to microinjection studies, in vivo and in vitro electrophysiological analyses of functionally identified neurons in cardiovascular-related CNS …