Abstract 1562: Increases of Immune Cells and their Related Cytokines in Blood and Spleen are Modulated by Chromosome 2 in Hypertensive Rats with an Activated Endothelin System
Adaptive immune cells are involved in development and/or maintenance of hypertension. Hypertension is a polygenic disease that can be modulated by chromosome 2 (chr2), which contains candidate genes for inflammatory responses. We hypothesized that chr2 up-regulates inflammatory responses in hypertensive rats (Dahl salt-sensitive-SS). We used Brown Norway strain (BN-normotensive rats), SS strain and consomic strain (SSBN2) that contains chr2 of BN rat in SS genetic background. Systolic blood pressure was higher in SS rats than BN and intermediate in SSBN2 (P<0.001). This correlated with increased aortic preproendothelin (ET)-1 mRNA content in SS compared to BN and SSBN2 (P<0.01). Plasma cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-10 and GM-CSF), measured by Bioplex assay, were increased in SS compared to BN and SSBN2 (P<0.001). Total number of immune cells was measured by FACS analysis. Leucocytes (expressing CD45) were increased in blood and spleen from SS compared to BN. This increase was reduced in spleen from SSBN2 (P<0.01). In the pool of CD45+ cells, CD3− cells were increased in blood and spleen from SS compared to BN and reduced in SSBN2 (P<0.05) compared to SS. Although the increase of CD3+ T cells in SS was not modified in SSBN2, further experiments identified an increase of CD3+ CD8+ cells in SS compared to BN and a greater increase in SSBN2 compared to SS (P<0.01). CD3+CD4+ cells were increased in the spleen in SS compared to BN and were reduced in SSBN2 compared to SS (P<0.05). To understand the meaning of the reduction of plasma cytokines and increase of CD3+CD8+ (related to pro-inflammatory responses), the CD25+ T cell population was studied. CD4+CD25+ T cells were increased in SS compared to BN and reduced in SSBN2 compared to SS. SSBN2 and SS exhibited the same increased levels in the blood and the spleen of CD8+CD25+ cells compared to BN (P<0.01). Our results show for the first time that 1) adaptive immune cells are increased in hypertensive rats with an activated ET system, 2) chr2 plays a role in inflammatory responses and 3) CD8+CD25+ cells are unaffected by reduction of blood pressure. This study identifies a genetic predisposition for inflammatory responses that could lead to the discovery of new target genes involved in hypertension on chr2.