Abstract 2529: Chromosome 2 and Vascular Inflammatory Responses
Microvascular inflammation contributes to the pathogenesis of cardiovascular disease and hypertension. The purpose of this study is to identify the contribution of chromosome 2 (chr2) to vascular inflammatory responses. We hypothesize that transfer of chr2 from normotensive rats (Brown Norway - BN) to hypertensive rats (Dahl salt-sensitive - SS), a model known as a consomic strain (SSBN2), allows recovery of the normal inflammatory response that might be altered in SS compared to BN. Results showed that SS rats exhibited a higher blood pressure than BN and SSBN2 (181±5 vs 122±12 and 154±11 mmHg respectively). Using ELISA-luminex assay, plasma cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-10 and TNFα) were increased in SS (P<0.001) compared to BN. SSBN2 exhibited reduced plasma IL-1α, IL-1β, IL-2 and IL-6 level compared to SS. To identify vascular smooth muscle cell (VSMC) contribution to cytokine production, the time-course of expression of cytokine mRNA and cytokine secretion in cultured VSMCs in response to angiotensin II (Ang II) was evaluated. IL-1α, IL-1β, IL-10, and TNFαproduction were not measurable in VSMCs from any strain. IL-6 production increased with AngII in a time-dependent manner in BN and SSBN2 but not in SS. Interestingly, IL-2 levels were higher (P<0.001) in SS than in BN and SSBN2. IL-2 protein levels were not affected by AngII. These observations demonstrate that chr2 plays a role in blood pressure regulation and systemic inflammation in salt-sensitive hypertensive rats. Furthermore, secretion of IL-2 by the microvasculature in salt-sensitive hypertensive rats is modulated by chr2. In conclusion, chr2 is involved in the vascular response of IL-2, and may play an important role in vascular inflammation in salt-sensitive hypertension.