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.

Fig. 1.

Effect of high-salt diet on systemic lupus erythematosus (SLE) disease activity. Plasma levels of dsDNA autoantibodies (Units/ml × 1,000) were significantly increased in SLE animals compared with controls (n = 12–18). High-salt diet did not significantly affect autoantibody production in control or SLE animals. *P < 0.05 vs. corresponding control.

Fig. 2.

Effect of high-salt diet on blood pressure during SLE. A: mean arterial pressure (mmHg) was significantly increased in SLE animals compared with controls (n = 8–14). High-salt diet did not affect mean arterial pressure in control or SLE animals. *P < 0.05 vs. corresponding control. B: rightward parallel shift in the pressure natriuresis relationship (salt intake in mmol/day vs. mean arterial pressure in mmHg) was observed in a subset of animals (n = 4–8).

Fig. 3.

Effect of high-salt diet on albuminuria during SLE: Urinary albumin excretion (mg/day) was increased in SLE animals compared with controls (n = 15–18). High-salt diet did not significantly increase albumin excretion in control or SLE animals.