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American Heart Association

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Final ID: TAC179

Ovarian Hormones Do Not Account For Maintained Diurnal Sodium Handling In Female Bmal1 KO rats

Abstract Body: Loss of circadian function is associated with development of hypertension and renal disease. Sodium excretion, a key factor in blood pressure regulation, is circadian controlled. Our lab has shown that male, but not female, rats lacking the core clock gene, Bmal1 (KO) exhibit a loss of diurnal sodium excretion rhythms. Estrogens are known to facilitate efficient renal sodium handling in females so we hypothesized that ovarian hormones account for sex differences in Bmal1 KO rats. Wildtype (WT) and KO rats were ovariectomized (OVX) or underwent sham surgery aged 10-13 weeks and housed in a 12L: 12D light schedule. At baseline the rats were fed normal salt (NS, 0.49% NaCl diet, ad lib) for 2 weeks then placed in metabolic cages to facilitate day/night urine collections. Rats were then placed on a high salt (HS) diet (4% NaCl diet, ad lib.) for two weeks ending again with metabolic cage measurements. OVX did not ablate Na+ excretion or aldosterone excretion rhythms in WT or KO rats. However, under baseline conditions KO OVX rats did excrete more Na+ (ptime= 0.002, post-hoc p =0.008) than SHAM controls despite no differences in aldosterone excretion. WT OVX and both SHAM groups maintained diurnal feeding and drinking behavior when fed NS. However, KO OVX only maintained diurnal drinking behavior but not feeding behavior (povx=0.011). WT rats on NS maintained diurnal urine volume rhythms while KO rats did not. Additionally, only KO SHAM rats displayed diurnal variation in urinary osmolarity (ptime=0.048, Tukey’s post hoc p=0.037). When fed HS, both WT and KO OVX rats excreted more Na+ in the active phase than SHAM controls (ptime<0.001, povx=0.023 for WT and ptime<0.001, povx= 0.048 in KO) despite no genotype differences in aldosterone excretion. All groups maintained rhythmic feeding and drinking behavior when fed HS diet. When fed HS, KO OVX animals drank more water only during the active phase compared to SHAM controls (povx=0.0212). When fed HS, all groups retained diurnal urine volume (ptime<0.001). Diurnal variation of urinary osmolarity was reversed in both WT OVX (ptime=0.037, post-hoc p=0.035) and KO rats (ptime<0.001). Overall, these data indicate that there are compensatory mechanisms in female rats unrelated to the actions of ovarian hormones that protect against loss of diurnal electrolyte excretion.
  • Venegas, Maria  ( University of Alabama , Birmingham , Alabama , United States )
  • Pollock, David  ( University of Alabama at Birmingham , Birmingham , Alabama , United States )
  • Author Disclosures:
    Maria Venegas: DO NOT have relevant financial relationships | David Pollock: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Poster Session 1 and Reception (includes TAC Poster Competition)

Thursday, 09/04/2025 , 05:30PM - 07:00PM

Poster Session

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