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ORIGINAL RESEARCH article

Front. Physiol.

Sec. Renal Physiology and Pathophysiology

This article is part of the Research TopicThe Role of the Nervous System in the Pathophysiology of Hypertension and Kidney DiseaseView all articles

2-Kidney-1-Clip Hypertension is not Attenuated in Mice Lacking the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Channel

Provisionally accepted
Sean  StockerSean Stocker*Isabella  BenoitIsabella BenoitJacob  B. SullivanJacob B. SullivanCaroline  B FerreiraCaroline B Ferreira
  • School of Medicine, University of Pittsburgh, Pittsburgh, United States

The final, formatted version of the article will be published soon.

Abstract Chemical ablation of renal sensory nerves using agonists for transient receptor potential vanilloid-1 (TRPV1) lowers arterial blood pressure (ABP) in multiple experimental models of hypertension including rats and mice. Recently, a direct role for TRPV1 channels was reported as male Trpv1-/- rats had a lower afferent renal nerve activity (ARNA) and arterial blood pressure (ABP) in a 2-kidney-1-clip (2K1C) renovascular hypertension. However, TRPV1 expression in sensory neurons differs across species with a lower level in mice versus rats or humans. Therefore, the current study assessed the proportion of TRPV1 renal sensory neurons in the mouse and also tested whether deletion of TRPV1 altered renovascular hypertension using wild-type (WT) and Trpv1-/- mice. 2K1C surgery was performed in mice by placement of a 0.5mm length of polyetrafluoroethylene tubing around the right renal artery. First, injection of the tracer wheat germ agglutinin conjugated to AlexaFluor 647 into the right kidney of C57Bl6J mice after sham or 2K1C surgery labeled neurons in the ipsilateral T10-L2 dorsal root ganglion. These neurons were small to medium sized (10-29um diameter). Importantly, approximately 60% were TRPV1-positive. Second, 2K1C surgery significantly increased ABP in both male and female WT and Trpv1-/- mice. However, the magnitude of the hypertension was not statistically different between strain and sex. Depressor responses to ganglionic blockade also did not differ between strains and sex. Altogether, these findings suggest that a subset of renal sensory neurons in the mouse are TRPV1-positive, and renovascular 2K1C hypertension is not attenuated in the Trpv1-/- mouse.

Keywords: Autonomic Nervous System, Blood Pressure, Hypertension, Dorsal root ganglion, Kidney, Renovascular

Received: 26 Sep 2025; Accepted: 12 Nov 2025.

Copyright: © 2025 Stocker, Benoit, Sullivan and Ferreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Sean Stocker, stockers@pitt.edu

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