Abstract 21: Sex Differences In Circadian Blood Pressure

Abstract

Hypertensive patients frequently show a lack of 10% decline in nighttime (or nondipping) blood pressure (BP), which is a strong predictor of a cardiovascular event. Clock genes are essential regulators in diurnal BP in the vasculature during hypertension. However, little is known if vascular circadian clock factors influence BP rhythms in a sex-dependent manner. To test the hypothesis that AngII-induced hypertension disrupts the expression pattern of peripheral clock genes, male and female C57Bl/6J mice were subjected to AngII (700 ng/kg/min) infusion for two weeks. BP was measured by radiotelemetry (N=7/group). After two weeks, the animals were sacrificed during daytime or nighttime, and aortas were assessed for expression of clock genes (Per1, Per2, Bmal1) and estrogen receptors (ERα and GPER). Two-way ANOVA was used to compare light-dark cycle and AngII treatment effects. Hypertensive females (MAP: day 121 ± 9 vs. night 126 ± 10 mmHg, P=0.39; 7.3% dipping) but not males (MAP: day 128 ± 3 vs. night 140 ± 2 mmHg, P=0.01; >10% dipping) developed a non-dipping phenotype. AngII-hypertension amplified the circadian pattern of Per1 in the male aorta but removed the Per1 circadian variation in the female aorta. AngII did not alter Per2 oscillation in the aorta of either sex. Bmal1 patterns were also amplified in males and reversed in females. In response to AngII, aortic ERα expression was augmented during the day in females (control 287 ± 14 vs. AngII 413 ± 42 copies/ng RNA; P=0.01) but not in males (P=0.34). Furthermore, GPER expression exhibited a circadian oscillation in control (day 9 ± 1 vs. night 20 ± 7.6 copies/RNA ng) and hypertensive males (day 12 ± 17 vs. night 20 ± 5 copies/RNA ng, P=0.04), but not in females. In conclusion, sex differences exist in non-dipping BP patterns and circadian disruption of estrogen receptors and clock genes Per1 and Bmal1 in the vasculature after AngII treatment. This data suggest that females may be more vulnerable to circadian disruption during hypertension.