title: 17β-Estradiol protects against the progression of hypertension during adulthood in a mouse model of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with a high prevalence of hypertension and cardiovascular disease. Because SLE predominantly affects women, estrogen is commonly implicated as a contributor to SLE disease progression. Using an established mouse model of SLE (female NZBWF1), we tested whether estrogen has a causal role in the development of hypertension in adulthood. Thirty-week-old SLE and control mice (NZW/LacJ) underwent either a sham or ovariectomy (OVX) procedure. 17β-Estradiol (E2; 5 μg/mouse, twice/week, subcutaneously) was administered to a subset of OVX mice. Mean arterial pressure (in mm Hg) was increased in SLE mice (134±4 versus 119±3 in controls). Contrary to our hypothesis, OVX exacerbated the hypertension in female SLE mice (153±3; P<0.05 versus SLE sham), and repletion of E2 prevented the OVX-induced increase in blood pressure (132±2). The prevalence of albuminuria was increased in SLE mice compared with controls (37% versus 0%). OVX increased the prevalence in SLE mice (70% versus 37% in SLE shams). Repletion of E2 completely prevented albuminuria in OVX SLE mice. Renal cortical tumor necrosis factor α was increased in SLE mice compared with controls and was further increased in OVX SLE. The OVX-induced increase in renal tumor necrosis factor α expression was prevented by repletion of E2. Treatment of OVX SLE mice with the tumor necrosis factor α inhibitor, etanercept, blunted the OVX-induced increase in blood pressure (140±2) and prevalence of albuminuria (22%). These data suggest that 17β-estradiol protects against the progression of hypertension during adulthood in SLE, in part, by reducing tumor necrosis factor α.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. mjryan@umc.edu.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Gilbert
authors.forename: Keisa W
authors.initials: KW
authors.lastname: Mathis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000378:metabolism; D051379:Mice; D016896:Treatment Outcome
chemical_list: D004967:Estrogens; D004958:Estradiol
keywords: estrogens; lupus erythematosus, systemic; pressure