Center of Arterial Hypertension, Cardiology Department, Austral University Hospital, Pilar, Argentina.
Am J Hypertens. 2010 Dec;23(12):1318-25. doi: 10.1038/ajh.2010.167. Epub 2010 Aug 12.
Renin-angiotensin system (RAS) modulation by high dietary sodium may contribute to salt-induced hypertension, oxidative stress, and target organ damage. We investigated whether angiotensin II (Ang-II) type 1 (AT1)-receptor blockade (losartan) could protect the aorta and renal arteries from combined hypertension- and high dietary salt-related oxidative stress.
Spontaneously hypertensive rats (3-month-old, n = 10/group) received tap water (SHR), water containing 1.5% NaCl (SHR+S), 1.5% NaCl and 30 mg losartan/kg/day (SHR+S+L), or 50 mg atenolol/kg/day (SHR+S+A). Atenolol was used for comparison. Ten Wistar-Kyoto rats (WKY) were controls. Systolic blood pressure (SBP) was determined by tail plethysmography. After 5 months of treatment, vascular remodeling and oxidative stress (superoxide production and NAD(P)H-oxidase activity (chemiluminescence), malondialdehyde (MDA) content (high-performance liquid chromatography), endothelial nitric oxide synthase (eNOS) activity [(14)C-arginine to (14)C citrulline], CuZn-SOD activity (spectrophotometry)) were studied.
In SHR, salt-loading significantly aggravated hypertension, urinary protein excretion, intraparenchymal renal artery (IPRArt) perivascular fibrosis, aortic and renal artery oxidative stress, and induced endothelial cell loss in IPRArts. In salt-loaded SHR, 5-month losartan and atenolol treatments similarly reduced SBP, but only losartan significantly prevented (i) urinary protein excretion increase, (ii) or attenuated hypertension-related vascular remodeling, (iii) aortic MDA accumulation, (iv) renal artery eNOS activity lowering, and (v) aortic and renal artery superoxide dismutase (SOD) activity reduction. In SHR+S, the contributions to aortic superoxide production were as follows: uncoupled eNOS > xanthine oxidase (XO) > NAD(P)H oxidase.
In this salt-sensitive genetic hypertension model, losartan protects from hypertension- and high dietary salt-related vascular oxidative stress, exceeding the benefits of BP reduction. Also, during salt overload, BP-independent factors contribute to vascular remodeling, at least part of which derive from AT1-receptor activation.
高膳食钠对肾素-血管紧张素系统（RAS）的调节可能导致盐诱导的高血压、氧化应激和靶器官损伤。我们研究了血管紧张素 II（Ang-II） 1 型（AT1）受体阻断剂（氯沙坦）是否可以保护主动脉和肾动脉免受高血压和高盐相关的氧化应激。
自发性高血压大鼠（3 个月龄，每组 10 只）给予自来水（SHR）、含 1.5%NaCl 的水（SHR+S）、含 1.5%NaCl 和 30mg/kg/天氯沙坦（SHR+S+L）或 50mg 阿替洛尔/千克/天（SHR+S+A）。阿替洛尔用于比较。10 只 Wistar-Kyoto 大鼠（WKY）为对照组。通过尾套测压法测定收缩压（SBP）。治疗 5 个月后，研究血管重构和氧化应激（超氧化物产生和 NAD（P）H-氧化酶活性（化学发光））、丙二醛（MDA）含量（高效液相色谱法）、内皮型一氧化氮合酶（eNOS）活性[（14）C-精氨酸至（14）C 瓜氨酸]、CuZn-SOD 活性（分光光度法））。
在 SHR 中，盐负荷显著加重高血压、尿蛋白排泄、肾内动脉（IPRArt）血管周围纤维化、主动脉和肾动脉氧化应激，并诱导 IPRArt 内皮细胞丢失。在盐负荷 SHR 中，5 个月的氯沙坦和阿替洛尔治疗同样降低 SBP，但只有氯沙坦显著预防（i）尿蛋白排泄增加，（ii）或减轻高血压相关的血管重构，（iii）主动脉 MDA 积聚，（iv）肾动脉 eNOS 活性降低，（v）主动脉和肾动脉超氧化物歧化酶（SOD）活性降低。在 SHR+S 中，主动脉超氧化物产生的贡献如下：脱偶联 eNOS＞黄嘌呤氧化酶（XO）＞NAD（P）H 氧化酶。
在这种盐敏感的遗传性高血压模型中，氯沙坦可防止高血压和高盐相关的血管氧化应激，其益处超过血压降低。此外，在盐超负荷期间，血压独立的因素导致血管重构，其中至少一部分源自 AT1 受体激活。
