The involvement of renal afferents in the maintenance of cardiorenal diseases

Abstract

Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared to total renal denervation. However more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.

Renal Nerve Activity and Arterial Depressor Responses Induced by Neuromodulation of the Deep Peroneal Nerve in Spontaneously Hypertensive Rats

“…This observation suggests that increasing both amplitude and pulse duration, additional renal axons are recruited. The renal nerve is known to play an important role in cardiovascular homeostasis ( Ricksten et al, 1979 ; Veiga et al, 2021 ), and it contains both efferent sympathetic and afferent sensory axons from the kidney to the dorsal root ganglia, which project centrally to the brain ( Leal et al, 2012 ; Mizuno et al, 2014 ; Pettigrew et al, 2017 ). It has been reported that denervation of the sinoaortic baroreceptors results in an immediate increase in RSNA, HR, and MAP ( Dibona and Jones, 2001 ).…”

A Closer Review of Therapeutic Effects of Renal Denervation on the Cardiorenal Syndrome: The Role of Classical and Non-Classical Renin-Angiotensin System Axes

“…One of the golden key players in the scenario of Cardiorenal Syndrome is the elevation of sympathetic vasomotor activity which has made this nervous system as one of the main therapeutic targets of this syndrome (15). Evidence shows that the sympathetic nerve system has a critical role in regulating body homeostasis, especially controlling body fluids and blood pressure (16,17).…”

Cardiorenal syndrome: long road between kidney and heart

“…Renal IRI leads to the development of cardiac hypertrophy (CH). In many other models, AKI can directly or indirectly induce acute cardiac dysfunction by increasing angiotensin levels (AT1, AT2, and ACE), local and systemic cytokines (TNF-α, ILs, and IFN-γ), arrhythmias, and other components [45,46], such as increasing the presence of local norepinephrine and increasing sympathetic activity [35,47].…”

“…In the figure, it is possible to see the therapies involved in the RAAS blockage: AT1 antagonists, ACR blockers, and renin inhibitors Some vasomotor sympathetic activity is a common characteristic of HF [48]. Therefore, the SNS is a relevant therapeutic target [47]. During HF, renal sympathetic nerve activity increases and causes renal norepinephrine accumulation and renin release, which induces renal vasoconstriction that may contribute to CRS.…”