Hypertension-induced metabolic dysregulation drives multi-organ circadian desynchrony in rats

Hypertension is frequently associated with metabolic strain, but the extent to which this overload translates into multi-organ circadian misalignment remains poorly understood. We employed high-fructose (HF) and DOCA-salt rat models and performed circadian analysis of behavioral, metabolic, hormonal, and molecular rhythms across the suprachiasmatic nucleus (SCN), heart, and liver under controlled light–dark conditions. Hypertensive rats exhibited elevated blood pressure, metabolic markers and norepinephrine levels. Further, fragmented locomotor activity; altered melatonin and corticosterone rhythms indicate sustained autonomic and endocrine stress. These disruptions were accompanied by tissue-specific alterations in clock gene expression, with Rev-erbα and Per2 desynchrony in central and peripheral organs. This reflects impaired temporal coupling between central pacemaker and peripheral oscillators. Accordingly, a progressive trajectory of circadian disruption is initiated by hypertension-induced metabolic stress, emanating from peripheral desynchrony toward central clock involvement and ultimately compromising whole-body rhythmic integrity. Therefore sustained hypertension precipitates a breakdown in circadian organization, wherein chronic metabolic and endocrine overload progressively uncouples central and peripheral clocks, leading to diminished rhythmic stability. In summary, our findings establish circadian disintegration as a fundamental pathological consequence of hypertension and underscore the therapeutic importance of temporal coherence to preserve cardiovascular health and prevent downstream complications.