title: Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic Nerve Activity and Blood Pressure.
abstract: 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 multifaceted 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 (2.5-10 mmol/L) produced concentration-dependent excitation of OVLT neurons. Additionally, these excitatory responses were intrinsic to OVLT neurons because hypertonic NaCl evoked inward currents, despite pharmacological synaptic blockade. In vivo single-unit recordings demonstrate that the majority of OVLT neurons (72%, 13/19) display concentration-dependent increases in neuronal discharge to intracarotid (50 μL/15 s) or intracerebroventricular infusion (5 μL/10 minutes) of hypertonic NaCl. Microinjection of hypertonic NaCl (30 nL/60 s) into the OVLT, but not adjacent areas, increased lumbar SNA, adrenal SNA, and arterial blood pressure in a concentration-dependent manner. Renal SNA decreased and splanchnic SNA remained unaffected. Finally, local inhibition of OVLT neurons with the GABAAreceptor agonist muscimol (24 nL/10 s) significantly attenuated the sympathoexcitatory and pressor responses to intracerebroventricular infusion of 0.5 mol/L or 1.0 mol/L NaCl. Collectively, these findings indicate that OVLT neurons detect changes in extracellular NaCl concentrations to selectively alter SNA and raise arterial blood pressure.
authors.affiliation: From the Department of Medicine, Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, PA (B.J.K., S.D.S.); and Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA (B.J.K., S.S.S., K.N.B.).
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Kinsman
authors.affiliation: From the Department of Medicine, Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, PA (B.J.K., S.D.S.); and Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA (B.J.K., S.S.S., K.N.B.).
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Simmonds
authors.affiliation: From the Department of Medicine, Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, PA (B.J.K., S.D.S.); and Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA (B.J.K., S.S.S., K.N.B.).
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.affiliation: From the Department of Medicine, Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, PA (B.J.K., S.D.S.); and Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA (B.J.K., S.S.S., K.N.B.). stockers@pitt.edu.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stocker
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000502:physiology; D066278:Organum Vasculosum / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D012965:Sodium Chloride
keywords: blood pressure; hypothalamus; osmoreceptor; sodium; sympathetic