Okuno Keisuke, Naito Yoshiro, Yasumura Seiki, Sawada Hisashi, Oboshi Makiko, Nishimura Koichi, Asakura Masanori, Ishihara Masaharu, Masuyama Tohru
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Heart Vessels. 2018 Jul;33(7):820-825. doi: 10.1007/s00380-018-1134-4. Epub 2018 Feb 7.
Hypertension is a major public health problem leading to death. To reduce the morbidity and mortality in patients with hypertension, it is crucial to develop a novel strategy for prevention of hypertension. We have currently reported an attempt at dietary iron intake restriction as non-pharmacological treatment of hypertension in patients with hypertension. However, it remains fully unknown whether dietary iron restriction prevents the development of hypertension. We investigated the influence of dietary iron restriction on the development of hypertension in weanling pre-hypertensive model rats. 3-week-old male stroke-prone spontaneously hypertensive rats (SHR-SP) were randomly divided into two groups and were given an ad libitum normal diet or an iron-restricted diet for 12 weeks. Blood pressure was progressively increased in SHR-SP according to growth, while dietary iron restriction attenuated the development of hypertension. Proteinuria was also increased in SHR-SP according to growth, whereas dietary iron restriction suppressed the increment of proteinuria. SHR-SP exhibited glomerulosclerosis and exacerbated renal interstitial fibrosis at 15 weeks old, indicating that SHR-SP developed hypertensive nephropathy in the adult stage; however, these changes were attenuated by dietary iron restriction. Gelatin zymography showed dietary iron restriction decreased both renal MMP-2 and MMP-9 activities in SHR-SP at 15 weeks old. Of interest, dietary iron restriction suppressed renal TGFβ-RI expression and Smad2 phosphorylation in SHR-SP. Furthermore, dietary iron restriction decreased renal fibrosis, renal MMP-2 and MMP-9 activities, renal TGFβ-RI expression, and Smad2 phosphorylation in rats with unilateral ureteral obstruction. Dietary iron restriction prevented the development of hypertension in weanling pre-hypertensive rats.
高血压是导致死亡的主要公共卫生问题。为降低高血压患者的发病率和死亡率，制定预防高血压的新策略至关重要。我们目前已报道尝试将限制膳食铁摄入作为高血压患者高血压的非药物治疗方法。然而，膳食铁限制是否能预防高血压的发生仍完全未知。我们研究了膳食铁限制对断奶前期高血压模型大鼠高血压发生发展的影响。将3周龄雄性易中风自发性高血压大鼠（SHR-SP）随机分为两组，分别给予自由采食的正常饮食或铁限制饮食12周。SHR-SP的血压随生长逐渐升高，而膳食铁限制减弱了高血压的发展。SHR-SP的蛋白尿也随生长增加，而膳食铁限制抑制了蛋白尿的增加。SHR-SP在15周龄时出现肾小球硬化并加剧肾间质纤维化，表明SHR-SP在成年期发展为高血压肾病；然而，这些变化因膳食铁限制而减弱。明胶酶谱分析显示，膳食铁限制使15周龄SHR-SP的肾MMP-2和MMP-9活性均降低。有趣的是，膳食铁限制抑制了SHR-SP肾TGFβ-RI表达和Smad2磷酸化。此外，膳食铁限制降低了单侧输尿管梗阻大鼠的肾纤维化、肾MMP-2和MMP-9活性、肾TGFβ-RI表达以及Smad2磷酸化。膳食铁限制可预防断奶前期高血压大鼠高血压的发生。
