The Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic Nerve Activity and Blood Pressure

摘要

High salt diet elevates NaCl concentrations in the cerebrospinal fluid to increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. The organum vasculosum of the lamina terminalis (OVLT) resides along the rostral wall of the third ventricle, lacks a complete blood-brain-barrier, and plays a pivotal role in body fluid homeostasis. Therefore, the present study used a multi-faceted approach to examine whether OVLT neurons of Sprague Dawley rats are intrinsically sensitive to changes in extracellular NaCl concentrations and mediate the sympathoexcitatory responses to central NaCl loading. Using in vitro whole-cell recordings, step-wise increases in extracellular NaCl concentrations (2.5–10mM) produced concentration-dependent excitation of OVLT neurons. Additionally, these excitatory responses were intrinsic to OVLT neurons as hypertonic NaCl evoked inward currents despite pharmacologic synaptic blockade. In vivo single-unit recordings demonstrate the majority of OVLT neurons (72%, 13/19) display concentration-dependent increases in neuronal discharge to intracarotid (50µL/15s) or intracerebroventricular infusion (5µL/10min) of hypertonic NaCl. Microinjection of hypertonic NaCl (30nL/60s) into the OVLT, but not adjacent areas, increased lumbar SNA, adrenal SNA, and ABP in a concentration-dependent manner. Renal SNA decreased, and splanchnic SNA remained unaffected. Finally, local inhibition of OVLT neurons with the GABAA receptor agonist muscimol (24nL/10s) significantly attenuated the sympathoexcitatory and pressor responses to intracerebroventricular infusion of 0.5M or 1.0M NaCl. Collectively, these findings indicate that OVLT neurons detect changes in extracellular NaCl concentrations to selectively alter SNA and raise ABP.