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Loss of lymphocyte‐specific adaptor protein, LNK, aggravates endothelial dysfunction in angiotensin II‐induced hypertension (669.9)
Author(s) -
McMaster William,
Saleh Mohamed,
Itani Hana,
Harrison David,
Madhur Meenakshi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.669.9
Subject(s) - medicine , angiotensin ii , endocrinology , phenylephrine , signal transducing adaptor protein , endothelial dysfunction , endothelium , cytokine , acetylcholine , blood pressure , receptor
LNK, a lymphocyte‐specific adaptor protein, is a negative regulator of hematopoiesis and endothelial cell signaling. LNK reduces cytokine production and cellular proliferation. Recent genome wide association studies have identified a non‐synonymous single nucleotide polymorphism in LNK that is associated with human hypertension (HTN). We previously found that in mice, loss of LNK is associated with a marked increase in blood pressure and enhanced aortic infiltration of T cells in response to angiotensin II (AngII) infusion. We hypothesized that this HTN is due in part to altered vascular reactivity. LNK ‐/‐ and wild type (WT) mice were treated with AngII or vehicle for two weeks and vascular reactivity was assessed. Aortic rings were pre‐constricted with phenylephrine and subsequent relaxations to acetylcholine (Ach) and nitroglycerin (NTG) were examined. Interestingly, relaxation responses to Ach in LNK ‐/‐ mice were shifted to the right, indicating impairment of endothelial‐dependent relaxation. The responses to NTG were not significantly altered between LNK ‐/‐ and WT aortic rings. Therefore, loss of LNK aggravates endothelial function in the setting of hypertension and may provide one mechanism by which LNK contributes to hypertension and the associated end organ damage.WT Sham WT AngII LNK ‐/‐ Sham LNK ‐/‐ AngII Ach‐Log(EC50) 6.87±0.12 6.60±0.10 6.33±0.11 5.88±0.10LNK ‐/‐ vs WT p = 0.01; Ang vs Sham p = < 0.0001 Data are mean ± SEM (n = 4‐6)