Parasympathetic nerves in the kidney pelvis contribute to blood pressure regulation

INTRODUCTION: The existence of parasympathetic innervation in the kidney has long been controversial. Recent anatomical studies have provided evidence supporting such innervation by demonstrating the presence of acetylcholine (ACh) metabolic enzymes and tracing a brain-kidney vagal axis. Although these findings confirm the anatomical pathway, the functional capacity of these nerves to release neurotransmitters remains unverified, and the physiological role of this pathway is still unknown. METHODS: We defined the innervation of the kidney pelvis by co-labeling sympathetic, parasympathetic, and sensory nerves. ACh receptors (AChRs) expression in the kidney pelvis was assessed through single-cell RNA sequencing (scRNA-Seq), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and fluorescent in situ hybridization. ACh release from the kidney nerves was monitored via fiber photometry with a genetically encoded ACh sensor. Optogenetic activation was employed to investigate the functional effects of kidney parasympathetic efferent and afferent pathways on blood pressure and heart rate. RESULTS: We identified multi-component innervation in the kidney pelvis, including sympathetic, parasympathetic, and sensory nerves. Moreover, muscarinic AChRs were found to be expressed in this region. Neurogenic ACh release from kidney nerves was also detected under resting conditions and following transmural stimulation. Furthermore, optogenetic activation of the vagal brain-kidney afferent pathway resulted in a decrease in blood pressure. CONCLUSIONS: The kidney pelvis receives dual autonomic innervation from both sympathetic and parasympathetic nerves. The vagal kidney afferents are involved in blood pressure regulation.