Salt Diet Influences Endothelin‐1 Signaling in Renal Sensory Nerves

Abstract

Renal denervation is an effective anti‐hypertensive treatment in both humans and many animal models. However, it is unclear if the benefits of renal denervation are due to severing of the efferent (motor) nerves, afferent (sensory) nerves, or both. Recently, we reported that total renal denervation lowered blood pressure and global sympathetic tone in a model of endothelin B receptor (ETB‐R) deficiency without affecting renal excretory function or sodium balance suggesting a role for the afferent nerves in mediating hypertension and sympathetic tone in this model. High salt diet and endothelin‐1 signaling sensitize afferent activity, but the long‐term consequences and mechanisms of afferent sensitization are still relatively unknown. Thus we hypothesized that changes in salt diet would alter the gene expression profiles in renal afferent nerves following a high or low salt diet or endothelin receptor antagonist treatment. We isolated dorsal root ganglia (DRG) that contain the cell bodies of renal afferent nerves from Sprague‐Dawley rats fed either normal salt (NS, 0.49% NaCl), low salt (LS, 0.04% NaCl), or high salt (HS, 4.0% NaCl) for three weeks, or normal salt with 10 mg/kg/d ABT‐627 (ETA‐R antagonist) or 30 mg/kg/d A‐192621 (ETB‐R antagonist) for one week for qRT‐PCR analysis. Rats fed HS diet had significantly elevated expression of brain‐derived neurotrophic factor compared to NS (5.9 ± 1.8 relative to NS; p=0.04, n=3–4/group) indicating that HS diet activates renal afferent nerves as has been previously reported. Animals fed LS diet were not significantly different than NS. Neither salt diet had a significant effect on endothelin‐1 expression in DRG. Surprisingly, both LS and HS diets decreased the expression of both ETA‐R (0.7 ± 0.01 relative to NS p=0.1 and 0.4 ± 0.2 relative to NS p=0.04; respectively) and ETB‐R (0.5 ± 0.03 relative to NS p<0.001; and 0.5 ± 0.1 relative to NS p<0.001; respectively). Antagonism of ETA‐R resulted in a 2.0 ± 0.3 fold increase in endothelin‐1 expression in DRG compared to NS (p=0.02), while ETB‐R blockade had no effect (p=0.99) compared to NS, suggesting that ETA‐R activity may suppress endothelin‐1 expression in renal afferent nerves. These data suggest that salt diet influences activity of renal afferent nerves and that endothelin‐1 signaling in afferent nerves may be important modulators of activity.Support or Funding InformationT32HL007457 to BKB; K99HL127178 to JSS; and P01HL136267 to DMPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.