Deletion of the TRPV1 channel attenuates afferent renal nerve responses to renal artery occlusion but not elevated renal pelvic pressure

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Main Authors: Jacob B. Sullivan, Leon J. DeLalio, Sean D. Stocker
Format: Artículo Open Access
Published: Wiley 2025
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author Jacob B. Sullivan
Leon J. DeLalio
Sean D. Stocker
author_facet Jacob B. Sullivan
Leon J. DeLalio
Sean D. Stocker
Jacob B. Sullivan
Leon J. DeLalio
Sean D. Stocker
collection Wiley Open Access
contents Deletion of the TRPV1 channel attenuates afferent renal nerve responses to renal artery occlusion but not elevated renal pelvic pressure Jacob B. Sullivan Leon J. DeLalio Sean D. Stocker The Journal of Physiology Abstract Renal sensory neurons widely express the transient receptor potential vanilloid type 1 (TRPV1). TRPV1 is a non‐selective cation channel responsive to mechanosensitive stimuli, temperature, pH and various chemical factors. The present study tested whether TRPV1 channels contribute to afferent renal nerve activity (ARNA) responses during renal artery occlusion, renal ischaemia and increased renal pelvic pressure using a Trpv1 −/− rat with a 26‐bp deletion in exon 3. Both male and female wild‐type (WT) and Trpv1 −/− littermates (8–12 weeks) were anaesthetized with Inactin and prepared for recording of ARNA and haemodynamics. First total renal artery occlusion (90 s) produced a biphasic ARNA response in WT rats characterized by an abrupt increase in ARNA at the onset of occlusion followed by a delayed and substantial increase in ARNA after 45 s. This delayed ARNA activation was significantly attenuated in Trpv1 −/− rats. Second, graded reductions in renal blood flow (25%, 50% and 75%, 90 s) produced flow‐dependent increases in ARNA, but these responses did not differ between WT and Trpv1 −/− rats. Third, increased renal pelvic pressure (5, 10 and 20 mmHg, 60 s) elevated ARNA in both strains; however, the magnitude of these responses did not differ between WT and Trpv1 −/− rats. Altogether, these data suggest TRPV1 channels play distinct roles in renal interoception and ARNA activation, which include chemosensitive stimuli during prolonged renal artery occlusion but not mechanosensitive stimuli during increased renal pelvic pressure or acute reduction in renal blood flow. image Key points Renal artery occlusion produced a biphasic increase in afferent renal nerve activity (ARNA) of wild‐type (WT) rats with an initial increase at occlusion onset followed by a substantial increase 45 s later. This latter phase was significantly attenuated in Trpv1 −/− rats. Partial reductions in renal artery blood flow (75%, 50% and 25% of baseline) produced flow‐dependent increases in ARNA that were similar between WT and Trpv1 −/− rats. ARNA responses to elevated renal pelvic pressure did not differ between WT and Trpv1 −/− rats. Renal pelvic infusion of the TRPV1 antagonist capsazepine attenuated ARNA responses to elevated renal pelvic pressure in both WT and Trpv1 −/− rats, suggesting actions of capsazepine independent of the TRPV1 channel. These findings suggest TRPV1 channels play distinct roles in renal interoception and ARNA activation, which include chemosensitive stimuli during prolonged renal artery occlusion but not mechanosensitive stimuli during increased renal pelvic pressure or acute reduction in renal blood flow. 10.1113/jp289721 http://creativecommons.org/licenses/by-nc-nd/4.0/
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spellingShingle Deletion of the TRPV1 channel attenuates afferent renal nerve responses to renal artery occlusion but not elevated renal pelvic pressure
Jacob B. Sullivan
Leon J. DeLalio
Sean D. Stocker
The Journal of Physiology
Deletion of the TRPV1 channel attenuates afferent renal nerve responses to renal artery occlusion but not elevated renal pelvic pressure Jacob B. Sullivan Leon J. DeLalio Sean D. Stocker The Journal of Physiology Abstract Renal sensory neurons widely express the transient receptor potential vanilloid type 1 (TRPV1). TRPV1 is a non‐selective cation channel responsive to mechanosensitive stimuli, temperature, pH and various chemical factors. The present study tested whether TRPV1 channels contribute to afferent renal nerve activity (ARNA) responses during renal artery occlusion, renal ischaemia and increased renal pelvic pressure using a Trpv1 −/− rat with a 26‐bp deletion in exon 3. Both male and female wild‐type (WT) and Trpv1 −/− littermates (8–12 weeks) were anaesthetized with Inactin and prepared for recording of ARNA and haemodynamics. First total renal artery occlusion (90 s) produced a biphasic ARNA response in WT rats characterized by an abrupt increase in ARNA at the onset of occlusion followed by a delayed and substantial increase in ARNA after 45 s. This delayed ARNA activation was significantly attenuated in Trpv1 −/− rats. Second, graded reductions in renal blood flow (25%, 50% and 75%, 90 s) produced flow‐dependent increases in ARNA, but these responses did not differ between WT and Trpv1 −/− rats. Third, increased renal pelvic pressure (5, 10 and 20 mmHg, 60 s) elevated ARNA in both strains; however, the magnitude of these responses did not differ between WT and Trpv1 −/− rats. Altogether, these data suggest TRPV1 channels play distinct roles in renal interoception and ARNA activation, which include chemosensitive stimuli during prolonged renal artery occlusion but not mechanosensitive stimuli during increased renal pelvic pressure or acute reduction in renal blood flow. image Key points Renal artery occlusion produced a biphasic increase in afferent renal nerve activity (ARNA) of wild‐type (WT) rats with an initial increase at occlusion onset followed by a substantial increase 45 s later. This latter phase was significantly attenuated in Trpv1 −/− rats. Partial reductions in renal artery blood flow (75%, 50% and 25% of baseline) produced flow‐dependent increases in ARNA that were similar between WT and Trpv1 −/− rats. ARNA responses to elevated renal pelvic pressure did not differ between WT and Trpv1 −/− rats. Renal pelvic infusion of the TRPV1 antagonist capsazepine attenuated ARNA responses to elevated renal pelvic pressure in both WT and Trpv1 −/− rats, suggesting actions of capsazepine independent of the TRPV1 channel. These findings suggest TRPV1 channels play distinct roles in renal interoception and ARNA activation, which include chemosensitive stimuli during prolonged renal artery occlusion but not mechanosensitive stimuli during increased renal pelvic pressure or acute reduction in renal blood flow. 10.1113/jp289721 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Deletion of the TRPV1 channel attenuates afferent renal nerve responses to renal artery occlusion but not elevated renal pelvic pressure
topic The Journal of Physiology
url https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP289721