Blood pressure in a hypertensive mouse model of SLE is not salt-sensitive

Abstract

Systemic lupus erythematosus (SLE) is a risk factor for hypertension. Previously, we demonstrated that an established mouse model of SLE (female NZBWF1 mice) develops hypertension with renal inflammation and oxidative stress, both characteristics known as contributing mechanisms to the development of salt-sensitive hypertension. On the basis of this model, we hypothesized that blood pressure in SLE mice would be salt-sensitive. Thirty-week-old female SLE and control mice (NZW/LacJ) were fed 8% high-salt (HS) diet or normal diet (0.4% salt) for 4 wk. Plasma levels of double-stranded DNA (dsDNA) autoantibodies, a marker of SLE disease activity, were increased in SLE mice compared with controls (472 ± 148 vs. 57 ± 17 U/ml × 1,000, P < 0.001). HS did not alter dsDNA autoantibody levels in SLE or control mice. Mean arterial pressure was increased in SLE mice compared with controls (132 ± 3 vs. 118 ± 2 mmHg, P < 0.001) and was not significantly altered by the HS diet in either group. Similarly, albuminuria was higher in SLE mice compared with controls (10.7 ± 9.0 vs. 0.3 ± 0.1 mg/day) but was not significantly increased in SLE or control mice fed a HS diet. In summary, blood pressure during SLE is not salt-sensitive, and the HS diet did not adversely affect SLE disease activity or significantly augment albuminuria. These data suggest that renal inflammation and oxidative stress, characteristics common to both SLE and models of salt-sensitive hypertension, may have diverging mechanistic roles in the development of hypertension.

Preventing Autoimmunity Protects Against the Development of Hypertension and Renal Injury

“…Blood pressure was recorded at the end of the 14-week protocol in conscious freely-moving mice as previously reported by our laboratory 9,10,12,14 .…”

“…Plasma levels of anti-double-stranded DNA (dsDNA) antibodies, a clinical hallmark of SLE, were measured at week 34 as previously described 9,11,12,14 and are presented as a positive antibody activity index per the manufacturer's instructions and as previously published 15 . An antibody activity less than 1 is considered negative, whereas activity greater than 1 is considered positive.…”

“…Albuminuria was determined in 24-hour urine samples either weekly using a dipstick assay or at the conclusion of the study by ELISA (presented as excretion rate in μg/day) as previously described 9,10,12,14,16 . Paraffin-embedded kidneys were stained with Periodic Acid Schiff (PAS) to assess glomerulosclerosis as previously described 17 and Masson's trichrome staining to assess tubulointerstitial fibrosis.…”

“…Using an established female mouse model of SLE that displays these same characteristics, our laboratory has previously reported on several factors that contribute to the hypertension during SLE including endothelial dysfunction 8 , impaired renal hemodynamic function 9,10 , inflammatory cytokines 11 , and oxidative stress 12 . In the present study, we tested the hypothesis that the development of autoimmune disease is the underlying factor that leads to the prevalent hypertension associated with SLE.…”

Effect of endothelial microRNAs on blood pressure homeostasis

“…Previous studies demonstrated that a high salt diet (8% NaCl) did not affect blood pressure homeostasis in different strains of either male or female mice such as C57BL/6, 129 and NZW/LacJ [25][26][27] . On the other hand, it has been shown that high salt containing water (2% NaCl) intake induced significant elevation of BP and HR two weeks after loading in C57BL/6 male mice 10) .…”