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Cited by 20Blood Pressure and Hypertension StudiesRenin-Angiotensin System StudiesNeuroscience of respiration and sleep

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

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Goodwill, Vanessa S., Terrill, Christopher, Hopewood, Ian, Loewy, Arthur D., Knuepfer, Mark M.·2017·Autonomic Neuroscience
DOI 10.1016/j.autneu.2016.09.015PMC PMC5362356
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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 500mOsm) into the left renal pelvis of conscious rats for two 2hours 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 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) 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.

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  • Afferent renal nerves are chemosensitive, and their activity increases after intra-pelvic or intra-arterial infusion of adenosine, bradykinin, substance P, prostaglandin E2 or hypertonic saline.

    “Afferent renal nerves are chemosensitive and increases in activity have been documented in response to both intra-pelvic and intra-arterial infusion of adenosine, bradykinin, substance P, prostaglandin E2 and hypertonic saline45,50–54.”

    From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [54]

    The Introduction describes renal afferent fibers as chemosensitive, and Results §3.2 reports increased afferent nerve activity after hypertonic saline was infused into the renal pelvis of anesthetized rats. The paper does not document increased activity after intra-arterial infusion or after infusion of adenosine, bradykinin, substance P, or prostaglandin E2. (LLM, conf=0.88)

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  • The rise in afferent activity after intra-pelvic hypertonic saline can be blocked by benzamil or amiloride, suggesting a link between pelvic ENaC activity and afferent renal nerve activation.

    “afferent activity after intra-pelvic infusion of hypertonic saline can be blocked by simultaneous infusion of benzamil or amiloride, which block the epithelial sodium channel (ENaC)54, suggesting a link between pelvic ENaC activity and the activation of afferent renal nerves.”

    From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [54]

    Results §3.2 reports that hypertonic saline increased afferent renal nerve activity in anesthetized rats and that simultaneous benzamil or amiloride significantly attenuated the increase. It does not report complete blockade of the nerve response, so “blocked” overstates the result. The Discussion (§4.4) also notes that these drugs can affect sodium sensors other than ENaC. (LLM, conf=0.88)

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Authors
Goodwill, V. S., Terrill, C., Hopewood, I., Loewy, A. D., & Knuepfer, M. M.
Affiliations
  • Saint Louis University (US)
  • Washington University in St. Louis (US)
Corresponding author
Knuepfer, Mark M.
ORCID
Venue
Autonomic Neuroscience
Publisher
Elsevier BV
Published
2017-05
Volume
204
Pages
35-47
ISSN
1566-0702 (ISSN-L)
DOI
10.1016/j.autneu.2016.09.015
PMC
PMC5362356
OpenAlex
W2522580487
Cited by
20
References
70
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2016: 1
FWCI
1.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Autonomic Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
St. Louis University (DA-017371)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
renal afferent nerves, hypertonic saline, essential hypertension, Fos-like immunoreactivity, nucleus tractus solitarius, lateral parabrachial nucleus, paraventricular nucleus, supraoptic nucleus, benzamil, amiloride, sodium balance, blood pressure regulation, fluid volume regulation
MeSH terms
Afferent Pathways, Animals, Blood Pressure, Brain, Heart Rate, Immunohistochemistry, Kidney, Male, Neurons, Afferent, Photomicrography, Saline Solution, Hypertonic, Sodium, Dietary, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Epithelial Sodium Channels

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