Blockade of transient receptor vanilloid channels prevents the sympathoexcitatory response to central NaCl infusion (683.3)

Abstract

Increased cerebrospinal fluid sodium concentration elevates sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt‐sensitive hypertension. Recent in vitro evidence suggests the brain senses changes in osmotic pressure through TRPV1 channels. The present study investigated whether the sympathoexcitatory response to increased cerebrospinal fluid NaCl was mediated by central TRPV1 channels. Male Sprague‐Dawley rats were anesthetized with Inactin and instrumented with a lateral intracerebroventricular (ICV) cannula. 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=4) prevented any change in lumbar SNA (106±3%), heart rate (4±6), and mean ABP (1±1mmHg). ICV injection of ruthenium red or SB366791 did not alter any variable. These findings suggest that central TRPV1 channels mediate the sympathoexcitatory response to acute increases in cerebrospinal fluid NaCl concentration.Grant Funding Source: Supported by NIH R01HL113270 and AHA Established Investigator Award