Chronic circadian stress impairs blood pressure and sodium homeostasis in a diet- and sex-specific manner

This study investigates the effects of environmental circadian disruption and high-fat diet (HFD) on cardiovascular and renal functions in Bmal1 knockout (KO) and wild-type (WT) rats. Under 12:12 light:dark conditions, Bmal1 KO males and females on a normal fat diet (NFD) exhibit lower mean arterial pressure (MAP) compared to WT. These genotype differences were attenuated after subjecting rats to a weekly 6hr advance in the 12:12 light:dark protocol to induce chronic circadian stress (CCS). CCS modestly elevated MAP in males, eliminating pre-existing genotypic differences, while in females, CCS had no significant effects on MAP and heart rate. Under HFD, genotype-based MAP differences are attenuated, and sex differences in heart rate are diminished. CCS further elevated MAP in male Bmal1 KO, accompanied by reduced blood pressure amplitude. Diurnal variations in sodium excretion are abolished post-CCS in both WT and Bmal1 KO males on HFD. In Bmal1 KO females, CCS combined with HFD disrupts sodium excretion rhythms thus eliminating the protective effects seen on NFD. These findings highlight the complex interplay between circadian regulation, dietary fat, and environmental stress in modulating cardiovascular and renal physiology. This study further supports a “two-hit hypothesis,” where CCS and HFD may synergistically disrupt sodium homeostasis and blood pressure circadian rhythms in both males and females.