Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response
Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response
复制标题
DOI：
10.1161/01.hyp.37.2.781
复制
发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Webb, RC
中科院分区：
文献类型：
--
作者：
Beswick, RA;Zhang, HF;Webb, RC
我们之前报道过盐皮质激素（醋酸去氧皮质酮[DOCA]）高血压大鼠单核细胞/巨噬细胞浸润、活性氧簇积累和核因子-kappaB（NF-kappaB）激活增加。我们测试了这一假设，即长期抗氧化剂管理抑制超氧化物积累，降低血压，并减少NF-κ B激活DOCA盐高血压大鼠。DOCA大鼠的收缩压较假手术大鼠显著升高，DOCA大鼠的主动脉环超氧阴离子（O-2（-））生成较假手术大鼠增加。此外，用吡咯烷二硫代氨基甲酸酯（PDTC）或4-羟基-2，2，6，6-四甲基哌啶氧基（Tempol）治疗DOCA大鼠可显著降低收缩压和主动脉超氧化物蓄积。与未处理的DOCA大鼠相比，用PDTC或Tempol处理的DOCA大鼠中单核细胞/巨噬细胞浸润也显著减少。NF-κ B结合活性在未处理的DOCA大鼠中显著高于假手术大鼠或PDTC或Tempol处理的DOCA大鼠。此外，与假手术相比，用Tempol处理的DOCA大鼠在NF-κ B结合活性方面没有表现出显著差异。这些结果表明，抗氧化剂降低收缩压，抑制肾NF-κ B结合活性，并部分减轻DOCA盐高血压肾单核细胞/巨噬细胞浸润。
We previously reported increased monocyte/macrophage infiltration, reactive oxygen species accumulation, and nuclear factor-kappaB (NF-kappaB) activation in mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertensive rats. We tested the hypothesis that prolonged antioxidant administration inhibits superoxide accumulation, lowers blood pressure, and reduces NF-kappaB activation in DOCA-salt hypertensive rats. DOCA rats exhibited a significant increase in systolic blood pressure compared with sham rats, Aortic rings from DOCA rats exhibited increased superoxide (O-2(-)) production compared with sham rats. In addition, the treatment of DOCA rats with pyrrolidinedithiocarbamate (PDTC) or 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) caused a significant decrease in systolic blood pressure and aortic superoxide accumulation. Monocyte/macrophage infiltration was also significantly decreased in DOCA rats treated with PDTC or Tempol compared with untreated DOCA rats. NF-kappaB-binding activity was significantly greater in untreated DOCA rats than in either sham rats or PDTC- or Tempol-treated DOCA rats. Also, DOCA rats treated with Tempol exhibited no significant difference in NF-kappaB-binding activity compared with sham. These results suggest that antioxidants attenuate systolic blood pressure, suppress renal NF-kappaB-binding activity, and partly alleviate renal monocyte/macrophage infiltration in DOCA-salt hypertension.