Hypertension and endothelial dysfunction in the pristane model of systemic lupus erythematosus

• Published in: Physiological reports Vol. 9; no. 3; pp. e14734 - n/a
• Main Authors: McClung, Daniel M., Kalusche, William J., Jones, Katie E., Ryan, Michael J., Taylor, Erin B.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc; Wiley
• Subjects: Acetylcholine; Age; Animals; Antibodies; Antibodies, Antinuclear - blood; Arterial Pressure; Arteries; Arthritis; Autoantibodies; Autoimmune diseases; Autoimmunity; Blood pressure; Cardiovascular disease; Cardiovascular diseases; CD4 antigen; CD8 antigen; Disease Models, Animal; endothelial dysfunction; Endothelium; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Female; Females; Flow cytometry; Hydrocarbons; Hypergammaglobulinemia; Hypertension; Hypertension - immunology; Hypertension - metabolism; Hypertension - physiopathology; Immune system; Immunoglobulin G; Immunological tolerance; Inflammation; Laboratory animals; Leukocytes (neutrophilic); Lupus; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocytes B; Lymphocytes T; Mice; Mice, Inbred C57BL; Neutrophils - immunology; Neutrophils - metabolism; Original Research; Physiology; Pristane; Psoriasis; Rheumatoid arthritis; Systemic lupus erythematosus; Terpenes; Thymocytes; Thymocytes - immunology; Thymocytes - metabolism; Thymus gland; Vasodilation; New Zealand; pristane; systemic lupus erythematosus; autoimmunity; autoantibodies; endothelial dysfunction; hypertension
• ISSN: 2051-817X
• DOI: 10.14814/phy2.14734

Autoimmune diseases such as psoriasis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) have high rates of hypertension and cardiovascular disease. Systemic lupus erythematosus is a prototypic autoimmune disorder that primarily affects women of childbearing age and is associated with a loss of self‐tolerance, autoreactive B and T lymphocytes, and the production of autoantibodies, especially to nuclear components. In this study, we hypothesized that the pristane‐inducible model of SLE would develop hypertension and vascular dysfunction as the disease progressed. To test this hypothesis, female C57BL/6 mice were administered PBS or pristane. Seven months after pristane administration, mice developed various autoantibodies, including anti‐dsDNA IgG, anti‐ssDNA IgG, and anti‐nRNP IgG, as well as hypergammaglobulinemia. Several other immunological changes, including increased circulating neutrophils and increased CD4−CD8− (double negative) thymocytes were also detected. Mean arterial pressure (MAP) was elevated in pristane‐treated mice when compared to PBS‐treated mice. In addition, second‐order mesenteric arteries from pristine‐treated mice had impaired relaxation to the endothelium‐dependent vasodilator acetylcholine compared to PBS‐treated mice. These data suggest that the immune system dysfunction present in the pristane model of lupus contributes to the development of hypertension and vascular dysfunction. Autoimmune diseases such as systemic lupus erythematosus have high rates of hypertension and cardiovascular disease. In this study, we induced lupus in female C57BL/6 mice with the hydrocarbon oil pristane. Seven months after pristane administration, mice developed various autoantibodies and other immunological changes indicative of lupus as well as elevated blood pressure and endothelial dysfunction in second‐order mesenteric arteries.