Beschreibung:
<jats:sec><jats:label /><jats:p>Hypertension is a major health concern throughout the world and is the leading contributor to cardiovascular‐related deaths. While drug‐based treatments exist, many patients are drug‐resistant while others do not adhere to their prescribed treatment. To combat these obstacles, clinical trials are currently underway investigating the efficacy of renal denervation (RDN) for the treatment of hypertension. While recent clinical trials support the concept that RDN is efficacious, it is nonspecifically destructive in nature, ablating both sympathetic (efferent) and sensory (afferent) renal nerves. Previous experiments from our group showed via afferent‐specific renal denervation that sensory nerves drive the development and maintenance of the DOCA‐Salt model of hypertension in rats. However, the roles that specific subtypes of sensory renal nerves play in regulating cardiovascular function in a non‐pathophysiological state remain to be elucidated. With this objective in mind, we use large volume tissue clearing and imaging techniques, as well as kidney‐targeted optogenetic modulation of TRPV1+ sensory fibers to better understand the anatomy and function of this subtype of sensory renal nerves.</jats:p><jats:p>While previous anatomical studies of sensory renal nerves have focused on the innervation of the pelvic wall, here we report a close anatomical relationship between renal glomeruli and sensory fibers. To the best of our knowledge, this has not been quantified previously. Approximately half of the glomeruli analyzed are in close proximity to CGRP+ and/or TRPV1+ sensory fibers. These fibers occasionally appear to penetrate Bowman’s capsules, and they often follow a periglomerular path, contrasting the arteriolar interactions describing sympathetic fibers. Based on these observations and the expression profiles of these sensory fibers, our working hypothesis is that they sense changes in glomerular function, such as glomerular pressure. Further ongoing experiments will directly test this hypothesis.</jats:p><jats:p>Furthermore, experiments investigating the roles of TRPV1+ renal sensory fibers in cardiovascular regulation and renal function are in progress. Using a custom‐designed optogenetic kidney cup, LED stimulation is applied to the renal cortex in transgenic mice that express channel rhodopsin in TRPV1+ nerve fibers. To define the functions of these fibers, we measure mean arterial pressure and cortical blood flow as physiological outputs of their optogenetic activation. Unilateral optogenetic stimulation applied to the cortex of the mouse kidney results in a decrease in renal cortical blood flow, no change in systemic arterial pressure, and therefore an increase in renal resistance. These results suggest that glomerular TRPV1+ renal sensory fibers may function in a novel sympathoexcitatory reflex.</jats:p></jats:sec><jats:sec><jats:title>Support or Funding Information</jats:title><jats:p>NIH SPARC Award 1U01DK116320‐02, 2018‐2019 MnDRIVE Fellowship</jats:p></jats:sec>