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American Heart Association

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Final ID: 048

Evidence that Bmal1 Regulates Time-of-Day Dependent Control of Autonomic Tone in Rats

Abstract Body: Brain and muscle ARNTL-like protein (Bmal1) is a critical component of the endogenous molecular clock and has downstream functions that contribute to blood pressure (BP) regulation in multiple target organs. BP exhibits a crucial circadian rhythm in patient populations and pre-clinical models, but the contribution of Bmal1 to mediators of BP, such as autonomic tone, has been assumed but not thoroughly investigated. This study hypothesized that Bmal1 contributes to the temporal variation in BP through time-of-day dependent changes in autonomic output. Bmal1-knockout rats and wild-type littermates (n=6 each) were instrumented with telemeters in the abdominal aorta and allowed to recover for 2 weeks post-surgery. To assess the contribution of autonomic tone to BP at different times of day, animals were given an i.p. injection of hexamethonium chloride (30 mg/kg) at zeitgeber times (ZT) 0, 4, 8, 12, 16, and 20; with a minimum of 2 days recovery time between each injection. BP was recorded continuously and divided into 5 second epochs to determine the maximal pressor response for 15 minutes post-injection. BP displayed a clear diurnal pattern in both genotypes. At ZT 0, WT rats had a maximal pressor response of 55.3±5.9 mmHg but KO rats had a significantly reduced maximal pressor response of 35.1±5.7 mmHg (p<0.05). At ZT12, the maximal pressor response was similar between genotypes (WT: 48.3±5.5 mmHg vs. KO 41.6±8.9 mmHg, p>0.05). Maximal pressor responses at ZT 4, 8, 16, and 20 were similar between WT and KO animals. These data suggest a temporal component to the contribution of the autonomic tone to BP regulation that may be mediated by Bmal1. It is worth noting that while the maximal pressor response to hexamethonium chloride was similar between genotypes at some timepoints, it is possible that the relative contributions of the parasympathetic or sympathetic nervous system may be altered by loss of Bmal1. Future studies will assess the balance of each arm of the autonomic system at different times of day using pharmacological inhibition.
  • Rhoads, Megan  ( University of Alabama at Birmingham , Bessemer , Alabama , United States )
  • Pollock, David  ( University of Alabama at Birmingham , Birmingham , Alabama , United States )
  • Author Disclosures:
    Megan Rhoads: DO NOT have relevant financial relationships | David Pollock: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Concurrent B: Neurogenic Mechanisms

Friday, 09/05/2025 , 01:30PM - 03:00PM

Oral Abstract Session

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