Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

Abstract

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

“…The basal tachycardia presented by mice with periodontitis corroborates the hypothesis of sympathetic overactivation. It is well established that sustained sympathetic overactivity has been associated with the development of end-organ damage, such as cardiac hypertrophy and deterioration of kidney function 39 . In this context, the finds of the current study support the notion of increased cardiovascular risk associated with gingival infection in the model evaluated.…”

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise

“…The effects of increased renal sympathetic nerve activity on renal perfusion and metabolism, which is acknowledged as a central actor in the pathogenesis of primary hypertension 29 and renovascular hypertension, 30 has been the subject of a large number of studies, and has been excellently reviewed in recent literature. 31,32 The innervation is predominantly adrenergic. Increased renal sympathetic nerve activity causes a reduction of the renal blood flow and GFR, and reduction of sodium and water excretion.…”

Renal Sympathetic Nerve-Derived Signaling in Acute and Chronic Kidney Diseases

“…NE released from the nerve terminals, together with co-transmitters, such as ATP and neuropeptide Y, regulate kidney function [35]. NE in the kidney is involved in a number of physiological processes, including control of renal blood flow, glomerular filtration rate, reabsorption of water, sodium, and other ions, and release of renin [6]. We recently found that renal nerve-derived NE signaling via α 2 -ARs, promotes renal inflammation and interstitial fibrosis [25,31].…”

“…The kidneys are abundantly innervated by both renal afferent sensory and efferent sympathetic nerves and communicate with the central nervous system via the sensory afferent nerves [6,7]. Increased renal afferent activity directly influences sympathetic outflow to the kidneys via efferent nerves [6][7][8].…”

“…Increased renal sympathetic nerve activity leads to increased renin secretion, increased renal tubular sodium reabsorption, and decreased renal blood flow [6,10,21]. Renal denervation (RDNx) is proposed as a therapeutic strategy used in treatment of resistant hypertension [8,21,22].…”