Abstract 241: Splenic T Regulatory Lymphocytes Are Reduced in Genetically Hypertensive Rats Associated with Central Sympathoexcitation
Background: Chronic inflammation plays a role in the pathogenesis of hypertension. Among the subsets of T lymphocytes, T regulatory lymphocytes (Tregs), which are immune suppressors of inflammatory responses, are reported to prevent angiotensin II (AngII)-induced hypertension and vascular injury. We hypothesized that Tregs play a critical role in the development and maintenance of hypertension. The aim of the present study was to determine whether Tregs are decreased in genetically hypertensive rats at both prehypertensive and established ages compared with those in normotensive rats, and if so, to examine whether blockade of brain AngII type 1 receptors (AT1R) affects Tregs in hypertensive rats.
Methods and Results: We examined Tregs in stroke-prone spontaneously hypertensive rats (SHRSP) at prehypertensive (5 week old) and established ages (12 week old) and age-matched normotensive Wistar-Kyoto rats (WKY). In both SHRSP and WKY, the transcription factor forkhead box P3 (Foxp3) mRNA expression levels were greater in the spleen than in other organs. However, Foxp3 mRNA and protein expression levels in the spleen were significantly lower in SHRSP than in WKY (Foxp3 mRNA: 0.47±0.03 vs. 1.02±0.03, protein: 0.39±0.02 vs. 0.66±0.03, n=6 for each, p<0.05). Flow cytometric analysis revealed that CD4+CD25+Foxp3+ cells (Tregs) in the spleen were significantly lower in SHRSP than in WKY (%Foxp3+ gated on CD4+CD25+ cells in the spleen; 45.4±1.4 vs. 58.1±2.0, n=3 for each, p<0.05). In addition, CD4+CD25+Foxp3+ cells in the spleen were lower in prehypertensive SHRSP, but not in the thymus. In hypertensive SHRSP, intracerebroventricular infusion of AT1R blocker (losartan, 1mg/kg/day for 2 weeks) reduced blood pressure and 24-hour urinary norepinephrine excretion, and upregulated Foxp3 mRNA expression levels in the spleen (0.44±0.04 vs. 0.31±0.02, n=3-4, p<0.05, vs. vehicle-treated SHRSP).
Conclusion: Our findings indicate that splenic Tregs are reduced in SHRSP at both prehypertensive and established hypertensive stages. These alterations may contribute to the development and maintenance of hypertension. Central sympathoinhibition increases the reduced splenic Tregs in SHRSP suggesting interaction between sympathetic hyperactivity and Tregs.
- © 2013 by American Heart Association, Inc.