title: Hypertension and impaired vascular function in a female mouse model of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women during their reproductive years. Although women with SLE have hypertension, the underlying mechanisms for this have not been examined. Despite the fact that inflammation is associated with altered endothelial and vascular function, the role of altered vascular function in the development of hypertension during SLE is unclear. In the present study, we tested whether a mouse model of SLE (NZBWF1) develops hypertension and examined whether increased blood pressure was associated with impaired endothelial-dependent relaxation. Female NZBWF1 mice were studied at 8, 20, and 36 wk of age. By 36 wk, urinary albumin and antinuclear antibodies were increased in SLE compared with control mice. Mean arterial pressure, measured by radiotelemetry, was significantly increased in SLE mice (124 +/- 4 mmHg, n = 10) compared with control NZW/LacJ mice (111 +/- 3 mmHg, n = 7) at 36 wk. Isolated carotid arteries from NZBWF1 mice, precontracted with U-46619 for assessment of endothelial-dependent relaxation, demonstrated a progressively impaired relaxation to ACh with age, although endothelial nitric oxide synthase mRNA expression was not different. Maximal tension generated by 5-hydroxytryptamine was increased in carotid arteries from NZBWF1 mice compared with controls at 8, 20, and 36 wk of age, suggesting a role for altered vascular function early on in the progression of SLE. Taken together, our data support a role for altered endothelial function as a contributing factor to the development of hypertension during SLE.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216, USA. mjryan@physiology.umsmed.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: Gerald R
authors.initials: GR
authors.lastname: McLemore
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000503:physiopathology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D009599:Nitroprusside / Q000494:pharmacology; D011507:Proteinuria / Q000652:urine; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D013931:Thromboxanes / Q000502:physiology; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000974:Antibodies, Antinuclear; D013931:Thromboxanes; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D012313:RNA; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine