title: Loss of endothelin B receptor function impairs sodium excretion in a time- and sex-dependent manner.
abstract: Recent studies suggested a direct link between circadian rhythms and regulation of sodium excretion. Endothelin-1 (ET-1) regulates sodium balance by promoting natriuresis through the endothelin B receptor (ETB) in response to increased salt in the diet, but the effect that the time of day has on this natriuretic response is not known. Therefore, this study was designed to test the hypothesis that ETBreceptor activation contributes to the diurnal control of sodium excretion and that sex differences contribute to this control as well. Twelve-hour urine collections were used to measure sodium excretion. On day 3 of the experiment, a NaCl load (900 μeq) was given by oral gavage either at Zeitgeber time [ZT] 0 (inactive period) or ZT12 (active period) to examine the natriuretic response to the acute salt load. Male and female ETB-deficient (ETBdef) rats showed an impaired natriuretic response to a salt load at ZT0 compared with their respective transgenic controls (Tg cont). Male ETBdef rats showed a delayed natriuretic response to a salt load given at ZT12 compared with male Tg cont, a contrast to the prompt response shown by female ETBdef rats. Treatment with ABT-627, an ETAreceptor antagonist, improved the natriuretic response seen within the first 12 h of a ZT0 salt load in both sexes. These findings demonstrate that diurnal excretion of an acute salt load 1) requires ET-1 and the ETBreceptor, 2) is more evident in male vs. female rats, and 3) is opposed by the ETAreceptor.
authors: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Jermaine G
authors: JG
authors: Johnston
authors: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Joshua S
authors: JS
authors: Speed
authors: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Chunhua
authors: C
authors: Jin
authors: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama dpollock@uab.edu.
authors: David M
authors: DM
authors: Pollock
mesh_terms: D000818:Animals; D000077868:Atrasentan; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000235:genetics*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D055647:Rats, Transgenic; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D013997:Time Factors
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044023:Receptor, Endothelin B; D012964:Sodium; D000077868:Atrasentan
keywords: ETA receptors; ETB receptors; circadian rhythm; kidney; male and female; rats