title: 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 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.
authors.affiliation: Department of Pharmacology and Physiology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Goodwill
authors.affiliation: Department of Pharmacology and Physiology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Terrill
authors.affiliation: Department of Pharmacology and Physiology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Hopewood
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Loewy
authors.affiliation: Department of Pharmacology and Physiology, St. Louis University School of Medicine, St. Louis, MO 63104, USA. Electronic address: knuepfmm@slu.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Knuepfer
mesh_terms: D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D007668:Kidney / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D010784:Photomicrography; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012982:Sodium, Dietary / Q000008:administration & dosage
chemical_list: D053503:Epithelial Sodium Channels; D016760:Proto-Oncogene Proteins c-fos; D012462:Saline Solution, Hypertonic; D012982:Sodium, Dietary
keywords: Arterial pressure regulation; CNS projections; Epithelial sodium channels (ENaCs); Fluid volume regulation; Hypertonic saline; Renal afferent nerves; c-fos activation