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.