Rodriguez-Iturbe Bernardo, Zhan Chang-De, Quiroz Yasmir, Sindhu Ram K, Vaziri Nosratola D
Renal Service and Laboratory, Hospital Universitario, Instituto de Investigaciones Biomédicas (Fundacite-Zulia), Universidad del Zulia, Maracaibo, Venezuela.
Hypertension. 2003 Feb;41(2):341-6. doi: 10.1161/01.hyp.0000052833.20759.64.
Previous studies have demonstrated that oxidative stress contributes to hypertension and treatments with either antioxidant or immunosuppressive/anti-inflammatory agents improve hypertension in spontaneously hypertensive rats (SHR). The present study was performed to determine if the antihypertensive effects of an antioxidant-rich diet are associated with reduction in the renal immune infiltration. Rats were divided into experimental groups (n=5 each) that were followed 7 months after birth, during which they were fed either a regular or antioxidant-enriched (test) diet as follows: SHR-R group=regular diet; SHR-T group=test diet throughout the experiment; SHR-S group=test diet for 4 months switched to regular diet thereafter; WKY group=control rats given regular diet. The SHR-T rats showed a significant reduction in systolic blood pressure (mm Hg): SHR-T=179.6+/-12.9 versus SHR-R=207.5+/-9.6 (P<0.001) and plasma hydrogen peroxide concentration (SHR-T=15+/-4 micro mol/L versus 34+/-9 in SHR-R rats). This was accompanied by significant reductions of renal tissue nitrotyrosine abundance, tubulointerstitial infiltration (cells/mm(2)) of lymphocytes (SHR-T=18+/-3 versus SHR-R=30+/-4, P<0.001), macrophages (SHR-T= 17+/-3 versus SHR-R=22+/-3), and angiotensin II-positive cells (SHR-T= 17+/-2 versus SHR-R=25+/-5, P<0.01). Results in the SHR-S group were intermediate between the SHR-R and SHR-T groups. The intensity of the infiltration of lymphocytes, macrophages, and angiotensin II-positive cells significantly correlated with systolic blood pressure. Thus, the present study demonstrates that an antioxidant-enriched diet reduces the renal interstitial inflammation and improves hypertension in SHR. These findings point to interrelation between oxidative stress and inflammatory reactivity in the pathogenesis of hypertension.
以往研究表明,氧化应激会导致高血压,而使用抗氧化剂或免疫抑制/抗炎药物进行治疗可改善自发性高血压大鼠(SHR)的高血压状况。本研究旨在确定富含抗氧化剂的饮食的降压作用是否与肾脏免疫浸润的减少有关。将大鼠分为实验组(每组n = 5),在出生后7个月进行跟踪观察,在此期间,它们分别喂食常规饮食或富含抗氧化剂的(测试)饮食,具体如下:SHR-R组 = 常规饮食;SHR-T组 = 在整个实验过程中喂食测试饮食;SHR-S组 = 先喂食4个月测试饮食,之后改为常规饮食;WKY组 = 给予常规饮食的对照大鼠。SHR-T大鼠的收缩压(mmHg)显著降低:SHR-T = 179.6±12.9,而SHR-R = 207.5±9.6(P < 0.001),血浆过氧化氢浓度也降低(SHR-T = 15±4微摩尔/升,而SHR-R大鼠为34±9)。同时,肾脏组织硝基酪氨酸丰度、淋巴细胞的肾小管间质浸润(细胞/mm²)(SHR-T = 18±3,而SHR-R = 30±4,P < 0.001)、巨噬细胞(SHR-T = 17±3,而SHR-R = 22±3)以及血管紧张素II阳性细胞(SHR-T = 17±2,而SHR-R = 25±5,P < 0.01)均显著减少。SHR-S组的结果介于SHR-R组和SHR-T组之间。淋巴细胞、巨噬细胞和血管紧张素II阳性细胞的浸润强度与收缩压显著相关。因此,本研究表明富含抗氧化剂的饮食可减轻SHR的肾脏间质炎症并改善高血压。这些发现表明氧化应激与高血压发病机制中的炎症反应之间存在相互关系。