Presenting Author University of Alabama at Birmingham
Blood pressure (BP) is a crucial physiological parameter that exhibits a circadian rhythm in healthy individuals. Loss of this rhythm is associated with morbidity and mortality. To determine the contribution of the molecular clock to BP regulation, we developed a rat strain with whole body loss of Bmal1 gene expression, a core component of the transcription/translation feedback loop known as the molecular clock. We previously reported that Bmal1-/- rats of both sexes have rhythmic BP, but lower than Bmal1+/+ controls. Given the importance of the renin-angiotensin system in BP control, we hypothesized that loss of Bmal1 may reduce plasma renin activity in the Bmal1-/- rat. For this experiment, male rats were housed in a 12:12h light/dark cycle with constant humidity and temperature. Water and food (0.49% NaCl) were available ad libitum. BP was measured by a telemetry transmitter implanted in the abdominal aorta of 10-week-old rats. After a 10-day surgical recovery period, BP was recorded for 2 minutes every 10 minutes at 1000 samples/second. Mean BP, assessed by cosinor analysis, was lower in male Bmal1-/- (MBP MESOR: 109±2 mmHg, n=9) animals compared to littermate Bmal1+/+ controls (MBP MESOR: 117±3 mmHg, n=8, plt;0.05, ANOVA). In a separate cohort of animals, plasma was collected from male Bmal1-/- rats and littermate Bmal1+/+ controls across the circadian day every four hours in groups of 2-6 at each time point starting at zeitgeber time (ZT) 0 (07:00) and ending at ZT 20. Plasma renin activity (PRA) and total prorenin/renin were measured by ELISA (name the kits used). PRA was similar between male Bmal1-/- and Bmal1+/+ rats during the light (Bmal1+/+: 1.4±0.5 vs Bmal1-/-: 2.5±0.6 ng/mL, p=0.21, Student’s t-test) and dark (Bmal1+/+:2.4±0.7 vs Bmal1-/-: 2.4±0.5 ng/mL, p=0.97, Student’s t-test) periods. Plasma total prorenin/renin was similar between Bmal1-/- and Bmal1+/+ rats during the light (Bmal1+/+: 8.8±1.7 vs Bmal1-/-: 6.9±0.7 ng/mL, p=0.36, Student’s t-test) and dark (Bmal1+/+: 2.7±1.3 vs Bmal1-/-: 5.2±1.7 ng/mL, p=0.27, Student’s t-test) periods. These data suggest that loss of Bmal1 does not directly affect systemic plasma renin activity or total prorenin/renin concentrations in the rat. Furthermore, the lowered blood pressure observed in rats lacking Bmal1 does not appear to be a result of systemic changes in circulating renin activity or concentration.
Support or Funding Information
This research was supported by AHA Postdoctoral Grant 827566 to MKR and NIH P01 HL136267 to DMP.
