Mild and Severe Hypertension Differentially Induce Internal Circadian Misalignment, Sleep–Wake Fragmentation, and Neurocardiac Desynchronization in Rats

Both hypertensive models established new blood pressure set points, with DOCA-salt rats stabilizing at severe hypertension levels.

• Mild and severe hypertension models were associated with increased neurohumoral load and autonomic imbalance.
• DOCA-salt rats exhibited significant melatonin suppression and sustained elevations of norepinephrine, vasopressin, corticosterone, and calcium.
• Marked fragmentation of sleep cycles was observed in DOCA-salt rats compared to control and high-fructose groups.
• Phase shifts in cardiac molecular rhythms indicated peripheral desynchronization despite preserved rhythms in the suprachiasmatic nucleus.
• Allostatic load analysis suggested an early burden in severe hypertension, with delayed increases in mild hypertension.
• Causal network modeling indicated a shift from melatonin regulation to neurohumoral dominance in hypertensive conditions.

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