Renal Hemodynamic Function is Impaired in Female Mice with SLE

Abstract

Systemic lupus erythematosus (SLE) is a chronic multi‐system autoimmune disease characterized by the presence of circulating autoantibodies, systemic and localized inflammation, prevalent hypertension, renal injury, and cardiovascular disease. Onset of the disease typically occurs in young women of child‐bearing age, a time when women are typically protected from cardiovascular risk factors like hypertension. Although kidney involvement is common to patients with SLE, and renal hemodynamic dysfunction is evident in patients with active renal disease, surprisingly little is known about early changes in renal hemodynamic function that may contribute to the pathogenesis of hypertension during autoimmune diseases. We hypothesize that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension.Female NZBWF1 mice, an established experimental model of SLE, and female NZW (control) mice were instrumented with carotid artery and jugular vein catheters to determine mean arterial pressure (MAP) and glomerular filtration rate (GFR) respectively at ages 15, 20, 28, 31, and 34 weeks (n>3 control/age, n>4 SLE/age). MAP was measured in conscious, freely‐moving mice. GFR was measured by the clearance of fluorescein isothiocyanate‐inulin (FITC‐inulin) after achieving steady state through continuous infusion.From 15 weeks of age to 34 weeks of age, there is a progressive increase in the levels of circulating autoantibodies in female mice with SLE, whereas autoantibodies are unchanged in control mice (Figure 1). Compared with control mice, female mice with SLE have higher MAP at 15, 20, 28, 31, and 34 weeks of age, with an increase in pressure that occurs by 34 weeks of age (Figure 2). GFR remains moderately higher in SLE mice compared with control mice until 28 weeks of age at which time GFR sharply declines in the mice with SLE (Figure 3). GFR is unchanged in control mice across all ages.These data suggest that changes in renal hemodynamic function occur in female SLE mice prior to changes in MAP suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.Support or Funding InformationVA Merit BX002604, American Heart Association Predoctoral 19PRE34380830, NIH P20GM104357, NIH 5U54GM115428, NIH 5P01HL051971This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.