OVLT Neuron Responses to Hypertonic NaCl and Mannitol Differ: Implications for Neural Regulation of Blood Pressure by NaCl

Abstract

Central infusion of hypertonic NaCl raises sympathetic nerve activity (SNA) and arterial blood pressure (ABP). These sympathoexcitatory pressor responses are largely attenuated by lesion or pharmacologic inhibition of sites along the lamina terminalis, namely the organum vasculosum of the lamina terminalis (OVLT). Canonically, OVLT seats brain osmoreceptors. However, central infusion of hypertonic osmolytes (eg. mannitol, sorbitol) does not raise ABP as greatly as central infusion of NaCl. Whether separate osmoreceptor versus sodium receptor mechanisms within OVLT distinguish these responses remains unknown. Therefore, we hypothesized that hypertonic NaCl and mannitol/sorbitol excite OVLT neurons by different mechanisms to regulate SNA and ABP. To assess this hypothesis, whole‐cell recordings were performed on OVLT neurons in adult rat brain slices. In current clamp, action potential (AP) frequency was measure at baseline (3–5min), during sequence‐randomized bath application of equi‐hyperosmotic NaCl (+7.5mM) or mannitol (+15mM) krebs buffers (3min), stimulus washout (5–10min), and sequence repetition with the alternate osmotic stimulus. In the majority of OVLT neurons (total n=19), AP frequency increased >25% from baseline in response to both (11/19) hypertonic NaCl (1.36±0.38 Hz to 2.44±0.55 Hz, p<0.001 compared to baseline) and mannitol (1.22±0.38 Hz to 1.79±0.43Hz, p<0.001). Interestingly, osmotically equivalent hypertonic NaCl and mannitol stimuli (+15mOsm) elicited quantitatively different responses in the same OVLT neuron. The increase in AP frequency appeared greater in response to NaCl (ΔAP frequency from baseline = 1.08±0.33 Hz) than mannitol (ΔAP frequency from baseline = 0.57±0.09 Hz, p=0.083). Smaller proportions of OVLT neurons were either excited by NaCl alone (4/19), mannitol alone (2/19), or non‐responsive to both stimuli (2/19). These results demonstrate differences in the response profiles of OVLT neurons to hypertonic NaCl and mannitol. In a parallel set of experiments, lumbar SNA, adrenal SNA and ABP were measured in anesthetized adult rats (n=3–4) in response to equi‐hyperosmotic intracerebroventricular (ICV) infusions (5μL/10min) of NaCl (1.0M) and sorbitol (2.0M). ICV infusion of NaCl versus sorbitol produced significantly greater increases in lumbar SNA (NaCl: +23±2%, sorbitol: +9±1%, p<0.05), adrenal SNA (NaCl: +9±2%, sorbitol: +4±4%, p<0.05), and ABP (NaCl: +12±2mmHg, sorbitol: 1±1mmHg, p<0.05). Collectively, these different OVLT response profiles may represent distinct osmoreceptor versus sodium receptor mechanisms and contribute to the contrasting effects of ICV NaCl versus other osmolytes on SNA and ABP.Support or Funding InformationThe research was supported by National Heart, Lung, and Blood Institute Grant HL‐113270 (S.D.S.) and NRSA 1F30HL131269‐01A1 (B.J.K.), as well as American Heart Association Established Investigator Grant (S.D.S.) and Great Rivers Predoctoral Fellowship 14PRE19530001 (B.J.K), .