Abstract 089: Deletion of Circadian Clock Associated Gene, Rfwd2 , Alters Rhythm in Blood Pressure Timing Without Changes in Salt-Sensitivity

Abstract

Healthy individuals display a diurnal blood pressure (BP) rhythm and salt-sensitivity increases the susceptibility for dysfunctional BP rhythms. Previously, bayesian modeling found that Rfwd2 gene was associated with circadian clock gene pathways in the Dahl Salt-sensitive rats (SS). SS rats lacking Rfwd2 were generated to test the hypothesis that Rfwd2 alters the circadian BP rhythm and salt-sensitivity in SS rats. Rfwd2 total knockout rats on the SS background are embryonic lethal, thus experiments utilized male Rfwd2 heterozygous SS ( Rfwd2 +/- ; n=6) and SS rats (n=8). All rats were maintained on Teklad (NIH-31) normal salt diet (NS; 0.4% NaCl) and then fed high salt diet (HS; 4% NaCl). BP was recorded via telemetry and systolic BP analyzed on days 4-7 of diet. On NS, the amplitude (difference between peak and mean) and mesor (rhythm-adjusted mean) were similar between genotypes. However, HS diet increased the amplitude (SS: 5.2 ± 0.4 to 9.3 ± 0.5, P<0.0001; Rfwd2 +/- : 3.7 ± 0.5 to 9.0 ± 0.5, P<0.0001) and mesor (SS: 147 ± 1.2 mmHg to 166 ± 1.7 mmHg, P<0.0001; Rfwd2 +/- : 150 ± 1.6 mmHg to 177 ± 3.1 mmHg, P<0.0001) in both genotypes. On HS, Rfwd2 +/- rats compared to SS had greater mesor (178 ± 3.1 mmHg vs. 166 ± 1.7 mmHg, P=0.003, respectively) and similar amplitude. Rfwd2 +/- had significant 1.4hr delay in trough (lowest value) SBP timing compared to SS within both salt diets (NS: P=0.005; HS: P=0.008). In addition, HS caused a delay in trough SBP timing in both genotypes. These results (figure) show that Rfwd2 has a role in trough BP timing, and the lack of this gene results in an exaggerated mesor on HS diet and a 1.4hr delay on NS and HS diets, which could potentially be coupled with renal injury.