Role of renal sensory nerves in physiological and pathophysiological conditions

Abstract

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

“…It is well known that the mammalian kidney contains several distinct classes of sensory mechanoreceptors and chemoreceptors (18,36) that transmit information to the central nervous system. Stimulation of afferent renal nerves has been shown to evoke alterations in sympathetic nerve activity and arterial blood pressure (31,44).…”

“…The excitatory influence may represent an activation of quiescent renal afferents in response to a variety of stimuli (35,36). There are multiple triggers in the HF condition that have the potential for increased activation of the renal afferent nerve activity, including reduced perfusion pressure, increased venous pressure, increased inflammation, and increased oxidative stress to name a few (18). It is possible that such excitatory influence mediated by renal afferents in the HF condition may also contribute to the underlying mechanism/s for the sympathoexcitation seen in HF.…”

Renal Sympathetic Denervation: Hibernation or Resurrection?

“…The activation of efferent renal sympathetic fibers enhances renin secretion and sodium reabsorption, induces renal vasoconstriction and reduces renal blood flow and glomerular filtration rate [12,13]. …”

Renal deafferentation: target for treatment of cardiovascular diseases involving sympathetic overactivity

“…Kidney function is known to be of primary importance in the long-term regulation and maintenance of arterial pressure (24). However, it is well documented that the autonomic nervous system also plays a critical role in the control of arterial pressure and in the pathogenesis of hypertension (1, 2, 36, 41), especially as it is able to modify renal function (19,29). The autonomic nervous system and kidney are linked through renal nerves that are composed of both efferent sympathetic and afferent sensory fibers (19,29).…”

“…However, it is well documented that the autonomic nervous system also plays a critical role in the control of arterial pressure and in the pathogenesis of hypertension (1, 2, 36, 41), especially as it is able to modify renal function (19,29). The autonomic nervous system and kidney are linked through renal nerves that are composed of both efferent sympathetic and afferent sensory fibers (19,29). Although considerable evidence exists suggesting an overexcitation of the sympathetic nervous system in conjunction with neurohormonal factors in the pathogenesis of resistant forms of hypertension, these data do not unequivocally demonstrate whether the effects on arterial pressure following renal denervation are mediated by efferent renal sympathetic nerves or afferent sensory nerves originating in the kidney.…”