Abstract P155: B Cells Are Not Necessary for the Developmentof Ang II-induced Hypertension and End-Organ Damage

Chronic inflammation characterized by vascular T cell and macrophage infiltration is associated with angiotensin II (Ang II)-induced hypertension and end-organ damage. However, the role of B cells in the development of hypertension is not well established. Elevated levels of serum immunoglobulins have been observed in experimental and human hypertension. Prior studies demonstrated that B-cell-activating factor receptor-deficient (BAFF-R -/- ) mice, which lack mature B cells, are protected from Ang II-induced hypertension and vascular remodeling. However, BAFF-R can be expressed on non-B cells as well. Thus, to further investigate the role of B cells in hypertension, we studied mice with targeted disruption of the membrane exon of the immunoglobulin μ heavy chain gene (μMT -/- ) that encodes the constant region of the IgM isotype. In these mice, B cells are arrested at the pre-B cell maturation stage. Serum immunoglobulins were undetectable at a 1:30,000 dilution in μMT -/- mice. Interestingly, μMT -/- mice exhibited similar blood pressure increase in response to 4 weeks of Ang II infusion compared to age-matched wild type (WT) mice (p=0.675). Flow cytometry of aortae from Ang II-treated μMT -/- mice demonstrated fewer CD45+ cells (p=0.047), similar levels of CD8+ and CD4+ T cells (p=0.631 and p=0.721 respectively), a trend for more F4/80+ monocytes/macrophages (p=0.2567), and virtually no CD19+ B cells (p=0.002) compared to WT mice. Endothelium-dependent vasodilatation to acetylcholine was comparable between μMT -/- mice and WT mice after Ang II treatment (p=0.223), however μMT -/- mice displayed enhanced endothelium-independent vasodilatation to sodium nitroprusside than WT mice (p=0.024). Urinary albumin/creatinine ratio was similar between Ang II-treated μMT -/- mice and WT mice (p=0.488), indicating similar renal damage. Taken together, μMT -/- mice are not protected from Ang II-induced hypertension, suggesting that B cells and immunoglobulin production are not critical for hypertension and the associated end-organ damage.