Abstract 034: Transient Receptor Potential Vanilloid-1 (TRPV1) Channels Mediate the Sympathoexcitatory and Pressor Responses to Central NaCl Stimulation

Abstract

Accumulating evidence indicates a high salt diet increases cerebrospinal fluid sodium concentration to elevate sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt-sensitive hypertension. Recent evidence suggests TRPV1 channels underlie the ability of the brain to sense changes in osmotic pressure. The present study investigated whether the sympathoexcitatory response to intracerebroventricular (ICV) infusion of hypertonic NaCl was mediated by central TRPV1 channels. In Inactin-anesthetized Sprague-Dawley rats, ICV infusion of 1M NaCl (n=8) significantly increased lumbar SNA (140±12%), heart rate (20±7bpm), and mean ABP (9±1mmHg). ICV pretreatment with the broad-spectrum TRPV channel blocker ruthenium red (5mM, 2uL, n=8) eliminated the sympathoexcitatory response to ICV 1M NaCl: lumbar SNA (106±5%), heart rate (-6±7bpm), and mean ABP (1±2mmHg). Similarly, ICV pretreatment with the selective TRPV1 channel antagonist SB366791 (3mM, 2uL, n=8) prevented any change in lumbar SNA (106±3%), heart rate (4±6), and mean ABP (1±1mmHg). ICV injection of ruthenium red or SB366791 alone did not alter any variable. Surprisingly, ICV infusion of 1M NaCl (1μL) produced similar pressor responses in wild-type versus TRPV1-/- mice (12±2 vs 11±2 mmHg, n>4). Pretreatment with SB366791 attenuated the pressor response in wild-type but not TRPV1-/- mice. In vitro patch clamp recordings of neurons in the ventral lamina terminalis reveal that increases in bath osmolality produced dose-dependent membrane depolarization (5 mOsm: 5.0±0.63 mV, 10 mOsm: 6.1±1.24 mV, 15 mOsm: 12.4±2.1; n=5, P<0.05) and increase discharge frequency (5 mOsm: 208±32%, 10 mOsm: 246±55%, 15 mOsm: 274±101%, 20 mOsm: 496±53%; n=5, P<0.05). These responses were attenuated by bath application of the broad spectrum TRPV blocker ruthenium red. Collectively, these observations suggest that central TRPV channels mediate changes in neuronal excitability and cardiovascular responses to central osmotic stimulation.