Parasympathetic Nerves Innervate The Renal Artery And Pelvis

In mammals,most visceral functions are regulated by the both sympathetic and parasympathetic nerves.The kidneys have rich innervation,and the sympathetic innervation of the kidneys have been widely studied and deeply understood.Whether the kidney has parasympathetic innervation has been controversial.In recent years,a series of physiological experiments have revealed the effects of acetylcholine on renal hemodynamics,water and salt metabolism and renal pelvic rhythm.Recently,in clinical trials,electrical stimulation of the renal nerves distinguished between sympathetic and parasympathetic effects evoked by renal nerves activity.However,anatomical evidence for the parasympathetic innervation of the kidney is lacking to date.Interpretation of new clinical phenomena and optimization of renal denervation strategies for the treatment of resistant hypertension require a further understanding of renal innervation patterns,especially those to the main renal artery.In response to these scientific questions and clinical demands,this thesis focused on the parasympathetic innervation of the kidney.The main contents are as follows:(1)Providing anatomical evidences for renal parasympathetic innervation.Through genetic labeling and multiplex immunostaining,combined with microdissection and optical imaging,this thesis identified the cholinergic nerves innervating the main renal artery,segmental renal artery,and renal pelvis wall for the first time.The expression of multiple acetylcholine receptor subtypes in the renal artery and its segmental branches were revealed by Single-cell transcriptome sequencing.Moreover,a vagal circuit that innervated the kidney was traced by three-dimensional imaging of the whole brain at the level of single cell resolution,combined with transgenic mice and recombinant virus.(2)Evaluating the effects of parasympathetic nerve activity on renal function.The varied responses of arterial pressure evoked by renal nerves activity were characterized by multi-site electrical stimulations around the main renal arteries.Using the designer receptors exclusively activated by designer drugs method,this thesis long-term activated cholinergic neurons in the dorsal nucleus of vagus nerve of awake mice,and found that the increase of parasympathetic nerves activity could cause the decrease of serum renin level.Moreover,optogenetics was used to specifically activate the renal cholinergic nerves and the twophoton imaging was used to monitor the hemodynamics in the renal cortex.The results suggested that the activation of renal parasympathetic nerves reduced the flow rate of blood cells in the renal cortical capillaries.Above all,this thesis provided significance anatomical evidences for the renal parasympathetic innervation by revealing the cholinergic innervating the kidney and tracing the vagal branches projecting to the kidney.In addition,the effects of parasympathetic nerves activity on blood pressure,serum renin level and renal cortex hemodynamics were evaluated by various physiological strategies.The newly findings may contribute to understanding of neural regulation of renal function.Moreover,further understanding of renal innervation paradigm may promote the improvement of renal denervation strategies in clinic.