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American Heart Association

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Final ID: P-353

Sexual dimorphism of blood pressure responses to angiotensin II in rats subjected to early life circadian stress

Abstract Body: Various forms of early life stress (ELS) lead to a greater risk of hypertension, but no studies have examined stress produced by circadian disruption. We hypothesize that circadian stress during adolescence will increase sensitivity to a hypertensive stimulus in adulthood recapitulating other models of early life stress (ELS). We exposed male and female rats 1-2 weeks post-weaning to 6-hour phase advances (shifts) in the light/dark cycle each week for 4 weeks. To assess whether the molecular clock contributes to the response to ELS, we performed these studies in both Bmal1 knockout (KO) rats and littermate wildtype (WT) controls, Bmal1 is a core circadian clock transcription factor. At 10-12 weeks of age, baseline mean arterial pressure (MAP) was measured (telemetry) followed by a 2-wk angiotensin II (AngII) infusion (250 ng/kg/min, s.c.). At baseline, non-ELS KO rats of both sexes had lower MAP compared to WT littermates, but this genotype effect was lost in ELS rats. Thus, exposure to circadian stress early in life has only a modest effect on baseline blood pressure in rats lacking Bmal1. AngII increased MAP in all groups but was significantly attenuated in male ELS rats compared to non-ELS controls of both genotypes (pstress = 0.039, pgenotype=0.979, pSxG=0.917, 2-way ANOVA), but this attenuation was not evident in female rats (pstress = 0.497, pgenotype=0.041, pSxG=0.772). We also observed a significant phase advance in peak MAP in male non-ELS rats of both genotypes that was absent in ELS males (pGenotype =0.030, pAngII <0.001, pAngIIxGT =0.025). In contrast, there were no significant differences in peak MAP time in any female rats. The response to AngII was attenuated in ELS male, but not female rats. These data do not support our original hypothesis that exposure to circadian stress during adolescence induces hypersensitization to Ang II in rats but does reveal an impact on the timing of peak MAP in male rats. We propose that the attenuated MAP response to AngII seen in male rats following exposure to specific types of circadian stress during the post-weaning period may pre-condition rats against a subsequent hypertensive stimulus.
  • Aponso, Hiruni  ( University of Alabama at Birmingham , Birmiham , Alabama , United States )
  • Latimer, Mary  ( UNIVERSITY OF ALABAMA BIRMINGHAM , Birmiham , Alabama , United States )
  • Rhoads, Megan  ( University of Alabama at Birmingham , Birmiham , Alabama , United States )
  • Pollock, David  ( University of Alabama at Birmingham , Birmingham , Alabama , United States )
  • Author Disclosures:
    Hiruni Aponso: DO NOT have relevant financial relationships | Mary Latimer: DO NOT have relevant financial relationships | Megan Rhoads: No Answer | David Pollock: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Poster Session 2

Friday, 09/06/2024 , 09:00AM - 10:30AM

Poster Session

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