Ryan Michael J, McLemore Gerald R
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R736-42. doi: 10.1152/ajpregu.00168.2006. Epub 2006 Aug 3.
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.
系统性红斑狼疮（SLE）是一种慢性自身免疫性炎症性疾病，主要影响处于生育年龄的女性。虽然患有SLE的女性会出现高血压，但其潜在机制尚未得到研究。尽管炎症与内皮和血管功能改变有关，但SLE期间血管功能改变在高血压发展中的作用尚不清楚。在本研究中，我们测试了SLE小鼠模型（NZBWF1）是否会发生高血压，并检查血压升高是否与内皮依赖性舒张功能受损有关。对8周、20周和36周龄的雌性NZBWF1小鼠进行了研究。到36周时，与对照小鼠相比，SLE小鼠的尿白蛋白和抗核抗体增加。通过无线电遥测测量，36周时SLE小鼠的平均动脉压（124±4 mmHg，n = 10）显著高于对照NZW/LacJ小鼠（111±3 mmHg，n = 7）。用U-46619预收缩后分离的NZBWF1小鼠颈动脉，用于评估内皮依赖性舒张功能，结果显示随着年龄增长，对乙酰胆碱的舒张反应逐渐受损，尽管内皮型一氧化氮合酶mRNA表达没有差异。在8周、20周和36周龄时，与对照相比，NZBWF1小鼠颈动脉中5-羟色胺产生的最大张力增加，表明血管功能改变在SLE进展早期起作用。综上所述，我们的数据支持内皮功能改变是SLE期间高血压发展的一个促成因素。
