Dietary Iron Restriction Prevents Hypertensive Cardiovascular Remodeling in Dahl Salt-Sensitive Rats
Dietary Iron Restriction Prevents Hypertensive Cardiovascular Remodeling in Dahl Salt-Sensitive Rats
复制标题
DOI：
10.1161/hypertensionaha.110.159681
复制
发表时间：
2011-03-01
期刊：
影响因子：
8.3
通讯作者：
Masuyama, Tohru
中科院分区：
文献类型：
--
作者：
Naito, Yoshiro;Hirotani, Shinichi;Masuyama, Tohru
铁蓄积与几种心血管疾病的发病机制有关。然而，铁限制(IR)对心血管疾病的预防作用仍然不清楚。我们研究了饮食IR对Dahl盐敏感大鼠心血管病理生理的影响及其机制。Dahl盐敏感大鼠给予正常或高盐(HS)饮食。另一组Dahl盐敏感大鼠喂饲含铁限制(HS+IR)的HS饮食11周。给予HS饮食的Dahl盐敏感大鼠出现高血压、心力衰竭，并在饮食11周后降低存活率。相反，IR可减缓高血压和心力衰竭的发展，从而提高存活率。饮食IR抑制HS大鼠的心血管肥大、纤维化和炎症。HS大鼠主动脉中Akt、AMP激活的蛋白激酶和内皮型一氧化氮合酶的磷酸化水平降低，而IR饮食可使其改善。HS大鼠主动脉细胞铁输入蛋白转铁蛋白受体1和铁储存蛋白铁蛋白H亚单位的表达上调。IR还可减轻HS组的蛋白尿和氧化应激增加。N(G)-硝基-L-精氨酸甲酯阻断IR的有益作用，降低HS+IR大鼠的存活率。饮食IR对盐诱导的高血压、心血管重塑和蛋白尿具有保护作用，其机制是通过抑制氧化应激，维持主动脉中Akt、AMP激活的蛋白激酶和内皮型一氧化氮合酶。IR可能是预防盐敏感型高血压患者HS所致器官损害的有效策略。(高血压。2011；57：497-504。)
Iron accumulation is associated with the pathogenesis of several cardiovascular diseases. However, the preventive effects of iron restriction (IR) against cardiovascular disease remain obscure. We investigated the effects of dietary IR on cardiovascular pathophysiology and the involved mechanism in Dahl salt-sensitive rats. Dahl salt-sensitive rats were provided either a normal or high-salt (HS) diet. Another subset of Dahl salt-sensitive rats were fed an HS with iron-restricted (HS + IR) diet for 11 weeks. Dahl salt-sensitive rats given an HS diet developed hypertension, heart failure, and decreased a survival rate after 11 weeks on the diet. In contrast, IR attenuated the development of hypertension and heart failure, thereby improving survival rate. Dietary IR suppressed cardiovascular hypertrophy, fibrosis, and inflammation in HS rats. The phosphorylation of Akt, AMP-activated protein kinase, and endothelial nitric oxide synthase was decreased in the aorta of HS rats, whereas they were ameliorated by the IR diet. Aortic expression of the cellular iron import protein transferrin receptor 1, and the iron storage protein ferritin H-subunit, was upregulated in HS rats. IR also attenuated proteinuria and increased oxidative stress in the HS group. N(G)-nitro-L-arginine methyl ester abolished the beneficial effects of IR and decreased survival rate in HS + IR rats. Dietary IR had protective effects on salt-induced hypertension, cardiovascular remodeling, and proteinuria through the inhibition of oxidative stress, and maintenance of Akt, AMP-activated protein kinase, and endothelial nitric oxide synthase in the aorta. IR could be an effective strategy for prevention of HS-induced organ damage in salt-sensitive hypertensive patients. (Hypertension. 2011;57:497-504.)