Abstract
Increased microglia activation and neuroinflammation within autonomic brain regions have been implicated in stress-induced hypertension (SIH). The circadian clock affects physiological cellular and biological processes, including blood pressure (BP) control, but the mechanisms remain unclear. Microglia possess endogenous timekeeping mechanisms regulate immune responses. Here, we explore whether SIH is associated with disrupted diurnal rhythms in microglia proinflammatory factors (PICs) releasing. We found that SIH exhibit diminished BP circadian rhythms, which showed non-dipper hypertension. Microglia isolated from the rostral ventrolateral medulla (RVLM) of SIH rats had aberrant PICs releasing and CLOCK rhythms, while microglia from control rats exhibited robust rhythms of PICs expression both ex vivo and in vivo. In the RVLM, stress upregulated CLOCK expression which is independent of time of day in comparison with that of control. We further identified that upregulated CLOCK depressed sirt1 expression thereby increased oxidative stress-related HMGB1-PICs releasing in microglia in RVLM of SIH rats. In conclusion, the disrupts intrinsic circadian rhythms of microglia-derived PICs releasing involves in pathogeneses of non-dipper hypertension in stressed rats.
Highlights
The aberrant rhythms CLOCK gene induced increased HMGB expression in microglia in the RVLM of stress-induced hypertension rats.
Aberrant CLOCK depressed sirt1 expression, which resulted in oxidative stress initiated inflammatory HMGB1 activation in microglia in RVLM of stress-induced hypertension rats.
The disrupts intrinsic circadian rhythms of microglia-derived inflammatory factor releasing in the RVLM involving in pathogeneses of non-dipper hypertension.