CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats

Abstract

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500 mOsm) into the left renal pelvis of conscious rats for two hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500 mOsmNaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1 μM) or amiloride (10 μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension.

Renal sympathetic denervation for resistant hypertension: where do we stand after more than a decade

“…Activation of renal sensory afferent fibers by a high sodium diet decreases efferent sympathetic signals, which increases urinary sodium excretion to maintain sodium homeostasis 19 . Experiments in rats demonstrated that normal saline had little effect on afferent nerve activity, while hypertonic NaCl elicited an increase in renal afferent nerve activity 29 . On the other hand, experimental evidence shows that the afferent signaling resulting from renal injury increases efferent renal sympathetic activity leading to hypertension 30 .…”

GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation

“…Adequacy of the anesthesia was confirmed by the lack of the response to paw pinches during the surgical procedure. The direct recording of ARNA with intrapelvic injections was performed as described previously [24,26,34,35]. Briefly, the left kidney was exposed through a retroperitoneal flank incision.…”

Is Aberrant Reno-Renal Reflex Control of Blood Pressure a Contributor to Chronic Intermittent Hypoxia-Induced Hypertension?

“…In contrast, R2 chemoreceptors are active in the resting state and are slowly-adapting insofar as their firing continues 15–20 min after death. They are activated by renal ischemia and by backflow of hypertonic or hyperosmotic urine (Recordati et al, 1980; Goodwill et al, 2017). Studies pointed toward a role for chemoreceptors in initiating an excitatory reno-renal reflex, which contributes to sympathoexcitation and blood pressure elevation (Calaresu et al, 1976; Recordati et al, 1978; Goodwill et al, 2017).…”

“…They are activated by renal ischemia and by backflow of hypertonic or hyperosmotic urine (Recordati et al, 1980; Goodwill et al, 2017). Studies pointed toward a role for chemoreceptors in initiating an excitatory reno-renal reflex, which contributes to sympathoexcitation and blood pressure elevation (Calaresu et al, 1976; Recordati et al, 1978; Goodwill et al, 2017). To distinguish the role of mechanoreceptors from that of chemoreceptors, an increase in renal pelvic pressure over a physiological range (2.5–10 mmHg) was utilized to activate the mechanoreceptors while a solution of 450 mM NaCl was used to stimulate the chemoreceptors (Kopp et al, 1998b; Wainford and Frame, 2017).…”