MELATONIN ABOLISHES RENAL INFILTRATION OF T LYMPHOCYTES IN A HIGH SALT DIET INDUCED HYPERTENSION MODEL

Abstract

Objective: Low grade inflammation and oxidative stress play a role in the pathogenesis of cardiovascular diseases, including hypertension (HTN). There is emerging evidence that the immune system, and particularly the adaptive immune response, may be involved in the triggering of these processes. In a previous study we demonstrated that melatonin prevents kidney damage in salt induced HTN model by decreasing oxidative stress. We hypothesized that this effect is involving the immunomodulation properties of melatonin. 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 (n = 8 each group). By the end of the treatment or when rats were considered ill with less than 24 hours survival, rats were sacrificed and kidneys were harvested for immediate lymphocytes isolation and characterization by FACS (CD3+CD4+ and CD3+CD8+) and for chemoatractants (vcam-1, cxcl10,cxcl1,cx3cl1,cxcl12,ccl3 and nrlp3) gene expression studies. Results: 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+ cells, 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 increased significantly mRNA expression of renal vcam-1, cxcl10,cxcl1, ccl3 and nrlp3 (2 ± 0.2, 2.4 ± 0.3, 3.1 ± 0.4, 2 ± 0.3, 1.6 ± 0.1, time fold, respectively, HSD vs. Ctrl, p < 0.5). The mRNA expression of cxcl10 and cxcl1, which are lymphocytes attractants, was significantly low in the melatonin treated group despite concomitant salt consumption. Conclusions: Treating HSD fed rats with melatonin is associated with decrease in some chemoatractants expression and with significantly lower renal T lymphocytes infiltration.