MELATONIN DECREASES T LYMPHOCYTES INFILTRATION TO THE KIDNEYS OF HIGH SALT DIET FED RATS BY RESYNCHRONIZATION OF THE KIDNEY CIRCADIAN CLOCK

Objective: Evidence suggested that abnormal immune response triggers inflammation and oxidative stress that leads to development of hypertension. We have shown previously that melatonin decreased oxidative stress in kidneys of salt induced hypertension rats. Blood pressure (BP) harbor a circadian pattern. We hypothesized that melatonin effect is mediated by its effect on circadian functions, which improve immune system response. Design and method: Dahl salt sensitive (DSS) rats were fed normal chow [control (Ctrl)], or high salt diet (HSD) or HSD and melatonin (Mel) (30/mg/kg/day) in their water for 8 weeks. BP was measured by intra-arterial telemetry device. By the end of the treatment, rats were sacrificed, and kidneys were harvested for immediate lymphocytes isolation and characterization by FACS (CD3+CD4+ and CD3+CD8+) and for main circadian clock genes expression studies. Results: HSD fed rats had significantly higher 24H BP (153±3 vs. 128±6 mmHg) and less dipping changes (4% vs. 11%) than control rats. Melatonin treatment decreased 24H BP (139±6 mmHg) and improve dipping (7%). HSD was associated with significant renal infiltration of CD4+ and CD8+ T lymphocytes compare to control (0.16±0.02 vs. 5.18±1.6 and 0.95±0.15 vs. 4.6±0.75, % of CD3+ cell, Ctrl vs. HSD, CD4+ and CD8+ respectively, p<0.05). Melatonin treatment significantly reduced renal lymphocytes infiltration (0.7±0.2 and 1.37±0.45% of CD3+ cells, CD4+ and CD8+ respectively, p<0.05 vs. HSD). HSD changed significantly mRNA expression of renal circadian genes (BMAL, Cry2 and Per1) while melatonin restores the expression of those genes toward control expression. Conclusions: Treating HSD fed rats with melatonin restore circadian gens expression levels and is associated with significant reduction of renal T lymphocytes infiltration.